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Shigeji Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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effect of ouabain on the afterhyperpolarization of slowly adapting Pulmonary Stretch Receptors in the rat lung
Brain Research, 2006Co-Authors: Shigeji Matsumoto, Chikako Saiki, Mamoru Takeda, Shinki Yoshida, Yumi KumagaiAbstract:Abstract In anesthetized, artificially ventilated rats with one vagus nerve section, the purposes of the present study were to investigate whether release from phasic consecutive hyperinflations (inflation volume = 3 tidal volumes) results in the afterhyperpolarization (AHP) of the slowly adapting Pulmonary Stretch receptor (SAR) activity and whether the effect of ouabain, a Na+–K+ ATPase inhibitor, alters AHP of the SAR activity seen after release from maintained inflations. Release from 10 consecutive phasic hyperinflations did not cause any significant inhibition of SAR activity. Release from maintained inflations (for approximately 10 and 15 cmH2O) for 5 s produced the induction of disappearance of SAR activity, corresponding with the AHP. Intravenous administration of ouabain (20 and 40 μg/kg) had no significant effects on the responses of SAR activity and SAR adaptation index (AI) to maintained inflations, but ouabain treatment with at 40 μg/kg resulted in a significant increase in the SAR activity after stopping the respirator and significantly attenuated the AHP of the SAR activity. In the immunohistochemical study, we found Na+–K+ ATPase α3-subunit-isoforms-like immunoreactivity in SAR terminals, forming leaflike extensions in the intraPulmonary bronchioles at different diameters, and those terminals were buried in the smooth muscle. In the same sections, the α1 subunit immunoreactivity of SAR terminals was not found. These results suggest that the mechanism of generating the AHP of SARs is mainly mediated by the activation of Na+–K+ ATPase α3 subunit isoform.
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the inhibitory effect of ouabain on the response of slowly adapting Pulmonary Stretch Receptors to hyperinflation in the rabbit
Life Sciences, 2005Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Yasuo Itoh, Yoshinobu Fujimi, Mamoru TakedaAbstract:Abstract The combined effects of ouabain (Na + –K + ATPase inhibitor) and hyperinflation (inflation volume = three tidal volumes) on slowly adapting Pulmonary Stretch Receptors (SARs) were studied before and after administration of nifedipine (an L-type Ca 2+ channel blocker) and KB-R7943 (a reverse-mode Na + –Ca 2+ exchanger blocker) in anesthetized, artificially ventilated rabbits after bilateral vagotomy. Before ouabain administration, hyperinflation stimulated SAR activity. After 20 min of ouabain administration (30 μg/kg) the SARs increased discharge rates in normal inflation. Under these conditions, hyperinflation initially stimulated SAR activity but subsequently inhibited the activity at peak inflation. Additional administration of 60 μg/kg ouabain (total dose = 90 μg/kg) caused a further stimulation of SAR activity, but 20 min later both normal inflation and hyperinflation resulted in a greater inhibition of the receptor activity. The hyperinflation-induced SAR inhibition in the presence of ouabain (30 μg/kg) was not significantly altered by administration of either nifedipine (2 and 4 mg/kg) or KB-R7943 (1 and 3 mg/kg). In another series of experiments, we further examined the combined effects of ouabain and hyperinflation in veratridine (a Na + channel opener, 40 μg/kg)-treated animals. After recovery from the veratridine effect on SAR activity, which vigorously stimulated the receptor activity, ouabain treatment (30 μg/kg) that silenced the receptor activity at peak inflation greatly inhibited hyperinflation-induced SAR stimulation. These results suggest that hyperinflation-induced SAR inhibition in the presence of ouabain may be related to a Na + overload, but not to a Ca 2+ influx via activation of L-type Ca 2+ channels, in the SAR endings.
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effects of acetazolamide and 4 aminoprydine on the responses of deflationary slowly adapting Pulmonary Stretch Receptors to co2 inhalation in the rat
Life Sciences, 2003Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Jun Kadoi, Mamoru TakedaAbstract:Abstract The inhibitory effect of CO 2 on deflationary slowly adapting Pulmonary Stretch Receptors (deflationary SARs) was investigated before and after administration of acetazolamide, a carbonic anhydrase (CA) inhibitor, or 4-aminopyridine (4-AP), a K + channel blocker, in anesthetized, artificially ventilated rats after unilateral vagotomy. CO 2 inhalation (maximum tracheal CO 2 concentration ranging from 9 to 12%) for approximately 60 s decreased the impulse activity of deflationary SARs but had no significant effect on tracheal pressure (P T ) as an index of bronchomotor tone. Acetazolamide treatment (20 mg/kg) diminished the inhibitory response of deflationary SARs to CO 2 inhalation. 4-AP (0.7 and 2.0 mg/kg) dose-dependently attenuated the decrease in deflationary SAR activity induced by CO 2 inhalation. When comparing the maximum attenuation due to 4-AP (2.0 mg/kg) and acetazolamide (20 mg/kg) in CO 2 -induced deflationary SAR inhibition, blockade of K + channels had a more pronounced effect. These results suggest that inhibition of deflationary SARs by CO 2 inhalation may be largely mediated by the stimulating action of 4-AP-sensitive K + currents in the nerve terminals of the Receptors.
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excitatory mechanism of deflationary slowly adapting Pulmonary Stretch Receptors in the rat lung
Journal of Pharmacology and Experimental Therapeutics, 2002Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The excitatory responses of deflationary slowly adapting Pulmonary Stretch receptor (SAR) activity to lung deflation ranging from approximately −15 to −25 cm of H 2 O for approximately 5 s were examined before and after administration of flecainide, a Na + channel blocker, and K + channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 μg/kg), an Na + channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other Receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na + channels on the nerve terminals of deflationary SARs.
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Effects of potassium channel and Na+-Ca2+ exchange blockers on the responses of slowly adapting Pulmonary Stretch Receptors to hyperinflation in flecainide-treated rats
British Journal of Pharmacology, 2001Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The effects of K+ channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na+ – Ca2+ exchange blocker, 2-[2-[4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), on the responses of slowly adapting Pulmonary Stretch receptor activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anaesthetized, artificially ventilated, unilaterally vagotomized rats after pretreatment with a Na+ channel blocker flecainide. The administration of flecainide (9 mg kg−1) at a dose greater than that which abolished 50 μg kg−1 veratridine-induced SAR stimulation also inhibited hyperinflation-induced stimulation of SARs. In flecainide-treated animals, administration of 4-AP (0.7 and 2 mg kg−1) stimulated SAR activity during normal inflation and also caused a partial blockade of hyperinflation-induced SAR inhibition. The discharges of SARs during normal inflation in flecainide-treated animals were not significantly altered by administration of either TEA (2 and 7 mg kg−1) or KB-R7943 (1 and 3 mg kg−1), but both K+ channel and Na+-Ca2+ exchange blockers partially attenuated hyperinflation-induced SAR inhibition. These results suggest that hyperinflation-induced SAR inhibition in the presence of flecainide (9 mg kg−1) involves the activation of several K+ conductance pathways. British Journal of Pharmacology (2001) 134, 682–690; doi:10.1038/sj.bjp.0704277
Mamoru Takeda - One of the best experts on this subject based on the ideXlab platform.
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effect of ouabain on the afterhyperpolarization of slowly adapting Pulmonary Stretch Receptors in the rat lung
Brain Research, 2006Co-Authors: Shigeji Matsumoto, Chikako Saiki, Mamoru Takeda, Shinki Yoshida, Yumi KumagaiAbstract:Abstract In anesthetized, artificially ventilated rats with one vagus nerve section, the purposes of the present study were to investigate whether release from phasic consecutive hyperinflations (inflation volume = 3 tidal volumes) results in the afterhyperpolarization (AHP) of the slowly adapting Pulmonary Stretch receptor (SAR) activity and whether the effect of ouabain, a Na+–K+ ATPase inhibitor, alters AHP of the SAR activity seen after release from maintained inflations. Release from 10 consecutive phasic hyperinflations did not cause any significant inhibition of SAR activity. Release from maintained inflations (for approximately 10 and 15 cmH2O) for 5 s produced the induction of disappearance of SAR activity, corresponding with the AHP. Intravenous administration of ouabain (20 and 40 μg/kg) had no significant effects on the responses of SAR activity and SAR adaptation index (AI) to maintained inflations, but ouabain treatment with at 40 μg/kg resulted in a significant increase in the SAR activity after stopping the respirator and significantly attenuated the AHP of the SAR activity. In the immunohistochemical study, we found Na+–K+ ATPase α3-subunit-isoforms-like immunoreactivity in SAR terminals, forming leaflike extensions in the intraPulmonary bronchioles at different diameters, and those terminals were buried in the smooth muscle. In the same sections, the α1 subunit immunoreactivity of SAR terminals was not found. These results suggest that the mechanism of generating the AHP of SARs is mainly mediated by the activation of Na+–K+ ATPase α3 subunit isoform.
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the inhibitory effect of ouabain on the response of slowly adapting Pulmonary Stretch Receptors to hyperinflation in the rabbit
Life Sciences, 2005Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Yasuo Itoh, Yoshinobu Fujimi, Mamoru TakedaAbstract:Abstract The combined effects of ouabain (Na + –K + ATPase inhibitor) and hyperinflation (inflation volume = three tidal volumes) on slowly adapting Pulmonary Stretch Receptors (SARs) were studied before and after administration of nifedipine (an L-type Ca 2+ channel blocker) and KB-R7943 (a reverse-mode Na + –Ca 2+ exchanger blocker) in anesthetized, artificially ventilated rabbits after bilateral vagotomy. Before ouabain administration, hyperinflation stimulated SAR activity. After 20 min of ouabain administration (30 μg/kg) the SARs increased discharge rates in normal inflation. Under these conditions, hyperinflation initially stimulated SAR activity but subsequently inhibited the activity at peak inflation. Additional administration of 60 μg/kg ouabain (total dose = 90 μg/kg) caused a further stimulation of SAR activity, but 20 min later both normal inflation and hyperinflation resulted in a greater inhibition of the receptor activity. The hyperinflation-induced SAR inhibition in the presence of ouabain (30 μg/kg) was not significantly altered by administration of either nifedipine (2 and 4 mg/kg) or KB-R7943 (1 and 3 mg/kg). In another series of experiments, we further examined the combined effects of ouabain and hyperinflation in veratridine (a Na + channel opener, 40 μg/kg)-treated animals. After recovery from the veratridine effect on SAR activity, which vigorously stimulated the receptor activity, ouabain treatment (30 μg/kg) that silenced the receptor activity at peak inflation greatly inhibited hyperinflation-induced SAR stimulation. These results suggest that hyperinflation-induced SAR inhibition in the presence of ouabain may be related to a Na + overload, but not to a Ca 2+ influx via activation of L-type Ca 2+ channels, in the SAR endings.
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effects of acetazolamide and 4 aminoprydine on the responses of deflationary slowly adapting Pulmonary Stretch Receptors to co2 inhalation in the rat
Life Sciences, 2003Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Jun Kadoi, Mamoru TakedaAbstract:Abstract The inhibitory effect of CO 2 on deflationary slowly adapting Pulmonary Stretch Receptors (deflationary SARs) was investigated before and after administration of acetazolamide, a carbonic anhydrase (CA) inhibitor, or 4-aminopyridine (4-AP), a K + channel blocker, in anesthetized, artificially ventilated rats after unilateral vagotomy. CO 2 inhalation (maximum tracheal CO 2 concentration ranging from 9 to 12%) for approximately 60 s decreased the impulse activity of deflationary SARs but had no significant effect on tracheal pressure (P T ) as an index of bronchomotor tone. Acetazolamide treatment (20 mg/kg) diminished the inhibitory response of deflationary SARs to CO 2 inhalation. 4-AP (0.7 and 2.0 mg/kg) dose-dependently attenuated the decrease in deflationary SAR activity induced by CO 2 inhalation. When comparing the maximum attenuation due to 4-AP (2.0 mg/kg) and acetazolamide (20 mg/kg) in CO 2 -induced deflationary SAR inhibition, blockade of K + channels had a more pronounced effect. These results suggest that inhibition of deflationary SARs by CO 2 inhalation may be largely mediated by the stimulating action of 4-AP-sensitive K + currents in the nerve terminals of the Receptors.
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excitatory mechanism of deflationary slowly adapting Pulmonary Stretch Receptors in the rat lung
Journal of Pharmacology and Experimental Therapeutics, 2002Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The excitatory responses of deflationary slowly adapting Pulmonary Stretch receptor (SAR) activity to lung deflation ranging from approximately −15 to −25 cm of H 2 O for approximately 5 s were examined before and after administration of flecainide, a Na + channel blocker, and K + channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 μg/kg), an Na + channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other Receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na + channels on the nerve terminals of deflationary SARs.
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effects of potassium channel and na ca2 exchange blockers on the responses of slowly adapting Pulmonary Stretch Receptors to hyperinflation in flecainide treated rats
British Journal of Pharmacology, 2001Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The effects of K+ channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na+ – Ca2+ exchange blocker, 2-[2-[4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), on the responses of slowly adapting Pulmonary Stretch receptor activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anaesthetized, artificially ventilated, unilaterally vagotomized rats after pretreatment with a Na+ channel blocker flecainide. The administration of flecainide (9 mg kg−1) at a dose greater than that which abolished 50 μg kg−1 veratridine-induced SAR stimulation also inhibited hyperinflation-induced stimulation of SARs. In flecainide-treated animals, administration of 4-AP (0.7 and 2 mg kg−1) stimulated SAR activity during normal inflation and also caused a partial blockade of hyperinflation-induced SAR inhibition. The discharges of SARs during normal inflation in flecainide-treated animals were not significantly altered by administration of either TEA (2 and 7 mg kg−1) or KB-R7943 (1 and 3 mg kg−1), but both K+ channel and Na+-Ca2+ exchange blockers partially attenuated hyperinflation-induced SAR inhibition. These results suggest that hyperinflation-induced SAR inhibition in the presence of flecainide (9 mg kg−1) involves the activation of several K+ conductance pathways. British Journal of Pharmacology (2001) 134, 682–690; doi:10.1038/sj.bjp.0704277
Chikako Saiki - One of the best experts on this subject based on the ideXlab platform.
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effect of ouabain on the afterhyperpolarization of slowly adapting Pulmonary Stretch Receptors in the rat lung
Brain Research, 2006Co-Authors: Shigeji Matsumoto, Chikako Saiki, Mamoru Takeda, Shinki Yoshida, Yumi KumagaiAbstract:Abstract In anesthetized, artificially ventilated rats with one vagus nerve section, the purposes of the present study were to investigate whether release from phasic consecutive hyperinflations (inflation volume = 3 tidal volumes) results in the afterhyperpolarization (AHP) of the slowly adapting Pulmonary Stretch receptor (SAR) activity and whether the effect of ouabain, a Na+–K+ ATPase inhibitor, alters AHP of the SAR activity seen after release from maintained inflations. Release from 10 consecutive phasic hyperinflations did not cause any significant inhibition of SAR activity. Release from maintained inflations (for approximately 10 and 15 cmH2O) for 5 s produced the induction of disappearance of SAR activity, corresponding with the AHP. Intravenous administration of ouabain (20 and 40 μg/kg) had no significant effects on the responses of SAR activity and SAR adaptation index (AI) to maintained inflations, but ouabain treatment with at 40 μg/kg resulted in a significant increase in the SAR activity after stopping the respirator and significantly attenuated the AHP of the SAR activity. In the immunohistochemical study, we found Na+–K+ ATPase α3-subunit-isoforms-like immunoreactivity in SAR terminals, forming leaflike extensions in the intraPulmonary bronchioles at different diameters, and those terminals were buried in the smooth muscle. In the same sections, the α1 subunit immunoreactivity of SAR terminals was not found. These results suggest that the mechanism of generating the AHP of SARs is mainly mediated by the activation of Na+–K+ ATPase α3 subunit isoform.
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the inhibitory effect of ouabain on the response of slowly adapting Pulmonary Stretch Receptors to hyperinflation in the rabbit
Life Sciences, 2005Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Yasuo Itoh, Yoshinobu Fujimi, Mamoru TakedaAbstract:Abstract The combined effects of ouabain (Na + –K + ATPase inhibitor) and hyperinflation (inflation volume = three tidal volumes) on slowly adapting Pulmonary Stretch Receptors (SARs) were studied before and after administration of nifedipine (an L-type Ca 2+ channel blocker) and KB-R7943 (a reverse-mode Na + –Ca 2+ exchanger blocker) in anesthetized, artificially ventilated rabbits after bilateral vagotomy. Before ouabain administration, hyperinflation stimulated SAR activity. After 20 min of ouabain administration (30 μg/kg) the SARs increased discharge rates in normal inflation. Under these conditions, hyperinflation initially stimulated SAR activity but subsequently inhibited the activity at peak inflation. Additional administration of 60 μg/kg ouabain (total dose = 90 μg/kg) caused a further stimulation of SAR activity, but 20 min later both normal inflation and hyperinflation resulted in a greater inhibition of the receptor activity. The hyperinflation-induced SAR inhibition in the presence of ouabain (30 μg/kg) was not significantly altered by administration of either nifedipine (2 and 4 mg/kg) or KB-R7943 (1 and 3 mg/kg). In another series of experiments, we further examined the combined effects of ouabain and hyperinflation in veratridine (a Na + channel opener, 40 μg/kg)-treated animals. After recovery from the veratridine effect on SAR activity, which vigorously stimulated the receptor activity, ouabain treatment (30 μg/kg) that silenced the receptor activity at peak inflation greatly inhibited hyperinflation-induced SAR stimulation. These results suggest that hyperinflation-induced SAR inhibition in the presence of ouabain may be related to a Na + overload, but not to a Ca 2+ influx via activation of L-type Ca 2+ channels, in the SAR endings.
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effects of acetazolamide and 4 aminoprydine on the responses of deflationary slowly adapting Pulmonary Stretch Receptors to co2 inhalation in the rat
Life Sciences, 2003Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Jun Kadoi, Mamoru TakedaAbstract:Abstract The inhibitory effect of CO 2 on deflationary slowly adapting Pulmonary Stretch Receptors (deflationary SARs) was investigated before and after administration of acetazolamide, a carbonic anhydrase (CA) inhibitor, or 4-aminopyridine (4-AP), a K + channel blocker, in anesthetized, artificially ventilated rats after unilateral vagotomy. CO 2 inhalation (maximum tracheal CO 2 concentration ranging from 9 to 12%) for approximately 60 s decreased the impulse activity of deflationary SARs but had no significant effect on tracheal pressure (P T ) as an index of bronchomotor tone. Acetazolamide treatment (20 mg/kg) diminished the inhibitory response of deflationary SARs to CO 2 inhalation. 4-AP (0.7 and 2.0 mg/kg) dose-dependently attenuated the decrease in deflationary SAR activity induced by CO 2 inhalation. When comparing the maximum attenuation due to 4-AP (2.0 mg/kg) and acetazolamide (20 mg/kg) in CO 2 -induced deflationary SAR inhibition, blockade of K + channels had a more pronounced effect. These results suggest that inhibition of deflationary SARs by CO 2 inhalation may be largely mediated by the stimulating action of 4-AP-sensitive K + currents in the nerve terminals of the Receptors.
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excitatory mechanism of deflationary slowly adapting Pulmonary Stretch Receptors in the rat lung
Journal of Pharmacology and Experimental Therapeutics, 2002Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The excitatory responses of deflationary slowly adapting Pulmonary Stretch receptor (SAR) activity to lung deflation ranging from approximately −15 to −25 cm of H 2 O for approximately 5 s were examined before and after administration of flecainide, a Na + channel blocker, and K + channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 μg/kg), an Na + channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other Receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na + channels on the nerve terminals of deflationary SARs.
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effects of potassium channel and na ca2 exchange blockers on the responses of slowly adapting Pulmonary Stretch Receptors to hyperinflation in flecainide treated rats
British Journal of Pharmacology, 2001Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The effects of K+ channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na+ – Ca2+ exchange blocker, 2-[2-[4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), on the responses of slowly adapting Pulmonary Stretch receptor activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anaesthetized, artificially ventilated, unilaterally vagotomized rats after pretreatment with a Na+ channel blocker flecainide. The administration of flecainide (9 mg kg−1) at a dose greater than that which abolished 50 μg kg−1 veratridine-induced SAR stimulation also inhibited hyperinflation-induced stimulation of SARs. In flecainide-treated animals, administration of 4-AP (0.7 and 2 mg kg−1) stimulated SAR activity during normal inflation and also caused a partial blockade of hyperinflation-induced SAR inhibition. The discharges of SARs during normal inflation in flecainide-treated animals were not significantly altered by administration of either TEA (2 and 7 mg kg−1) or KB-R7943 (1 and 3 mg kg−1), but both K+ channel and Na+-Ca2+ exchange blockers partially attenuated hyperinflation-induced SAR inhibition. These results suggest that hyperinflation-induced SAR inhibition in the presence of flecainide (9 mg kg−1) involves the activation of several K+ conductance pathways. British Journal of Pharmacology (2001) 134, 682–690; doi:10.1038/sj.bjp.0704277
Tsuyoshi Shimizu - One of the best experts on this subject based on the ideXlab platform.
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inhibitory mechanism of co2 inhalation on slowly adapting Pulmonary Stretch Receptors in the anesthetized rabbit
Journal of Pharmacology and Experimental Therapeutics, 1996Co-Authors: Shigeji Matsumoto, H Okamura, Kazunori Suzuki, N Sugai, Tsuyoshi ShimizuAbstract:The inhibitory effects of CO2 on slowly adapting Pulmonary Stretch Receptors (SARs) were studied before and after administration of acetazolamide, a carbonic anhydrase inhibitor, or nifedipine, a calcium channel blocker, in anesthetized, artificially ventilated rabbits after vagus nerve section. CO2 inhalation (maximal tracheal CO2 concentration ranging from 7.2% to 9.5%) for approximately 60 sec decreased the receptor activity during both inflation and deflation. The magnitude of decreased receptor activity during deflation became more pronounced than that seen during inflation. Acetazolamide treatment (20 mg/kg) diminished the inhibitory responses of slowly adapting Pulmonary Stretch Receptors to CO2 inhalation, which were not significantly influenced by pretreatment with nifedipine (1 mg/kg). Furthermore, CO2 inhalation before and after vagal denervation had no effect on total lung resistance and dynamic lung compliance. In another series of experiments, the staining to determine the presence of carbonic anhydrase enzymatic reaction was not found in the smooth muscle of either extraPulmonary or intraPulmonary bronchi. These results suggest that CO2-induced inhibition of slowly adapting Pulmonary Stretch Receptors is not related to the change in bronchomotor tone.
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the response of rapidly adapting Pulmonary Stretch Receptors elicited by sodium cyanide is augmented by vagotomy in the rabbit
Journal of The Autonomic Nervous System, 1995Co-Authors: Shigeji Matsumoto, Tsuyoshi ShimizuAbstract:Abstract The responses of rapidly adapting Pulmonary Stretch receptor (RAR) activity, tidal volume (VT), inspiratory airflow (VI), transPulmonary pressure (Ptrans) and dynamic lung compliance (Cdyn) to administration of NaCN (20 and 40 μg/kg) were compared before and after vagal section in anesthetized, spontaneously breathing rabbits. The responses of RARs were recorded from a partially dissected branch of the left vagus nerve (LVN). Before vagal section, hyperpnea following NaCN administration led to increases in RAR activity, VT, VI and Ptrans, but caused a decrease in Cdyn. Those responses obtained became more prominent by increasing the dose of NaCN. Under these conditions the increased receptor activity fired throughout the whole respiratory cycle. The responses of RAR activity, VT and Ptrans to NaCN administration were augmented by a vagal section that was produced by denervating the rest of the LVN still intact and right vagus nerve, and the discharge of Receptors showed a predominantly inspiratory pattern that corresponded to augmentation of both Ptrans and VT. Vagal section, however, had no significant effect on the changes of VI and Cdyn induced by NaCN. In addition, mean percent changes of increased VT and Ptrans produced by NaCN administration after vagal section were similar to those before vagal section. Furthermore, augmentation of VT and elevation in baseline VT, when NaCN after bilateral vagotomy was administered i.v., were preceded by simultaneously increased Ptrans and RAR activity. These results suggest that augmentation of NaCN-induced RAR stimulation in animals without intact vagus nerves is related to concomitant changes in the respiratory mechanics such as Ptrans and VT, probably involving the increased sensitivity of Receptors to these two factors.
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Effects of veratridine and nifedipine on ammonia-induced rapidly adapting Pulmonary Stretch receptor stimulation in vagotomized rabbits
Journal of The Autonomic Nervous System, 1994Co-Authors: Shigeji Matsumoto, Takahiro Kanno, Masao Yamasaki, Tadanori Nagayama, Tsuyoshi ShimizuAbstract:Abstract We studied the effects of aerosol administration of veratridine (a sodium channel opener) or nifedipine (a calcium channel blocker) on the responses of rapidly adapting Pulmonary Stretch Receptors (RARs) and dynamic lung compliance (Cdyn) to aerosols of 2 and 4% ammonia solutions in anesthetized spontaneously breathing rabbits without intact vagi. The RARs increased their activity following ammonia aerosol, and the increase was concentration-dependent. However, ammonia aerosol did not significantly alter the value of Cdyn. The RARs following aerosol administration of veratridine (about 200 μg) showed their characteristic firing pattern with several phases; each phase was characterized by the long high-frequency continuous discharges. Under these conditions, the response was not associated with any significant change in Cdyn. Even though the change in receptor activity produced by veratridine was restored to control level, subsequent aerosol application of ammonia led to similar firing patterns, as veratridine was given by aerosol, but had no significant effect on Cdyn. Following aerosol administration of nifedipine (about 1 and 2 mg) the RAR activity and Cdyn were similar to those during control. Furthermore, the ammonia-induced RAR stimulation was not significantly affected by nifedipine aerosol. These results suggest that the stimulation of RARs by ammonia in vagotomized rabbits is independent of changes in Cdyn and speculate that their excitatory effect is at least in part related to the activation of Na+ influx to the receptive terminals but is not involved in the secondary entry of Ca2+ ions to the receptor membrane, through voltage-dependent calcium channels.
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effects of isoprenaline on the responses of slowly adapting Pulmonary Stretch Receptors to reduced lung compliance and to administered histamine
Neuroscience Letters, 1994Co-Authors: Shigeji Matsumoto, Tsuyoshi ShimizuAbstract:Abstract To define the difference between the reponses of slowly adapting Pulmonary Stretch Receptors (SARs) to reduced dynamic lung compliance (Cdyn) and to administered histamine, experiments were performed in open-chest, artificially ventilated, bilaterally vagotomized rabbits with positive end-expiratory pressure (PEEP). Both stimuli caused an increase in tracheal pressure and produced augmentation of SAR activities during inflation and deflation. Isoprenaline treatment that blocked the responses of SARs and P T to histamine had no effect on those to reduced Cdyn. The results suggest that the response characteristics of SARs provoked by histamine administration do not involve the contribution of decreased Cdyn.
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Effects of calcium channel and H_1-receptor blockers on the responses of slowly adapting Pulmonary Stretch Receptors to histamine in vagotomized rabbits
Lung, 1993Co-Authors: Shigeji Matsumoto, Takahiro Kanno, Masao Yamasaki, Tadanori Nagayama, Tsuyoshi ShimizuAbstract:We studied the effects of calcium channel antagonists (verapamil and nifedipine) and H_1-receptor blockers (mequitazine) on changes in the slowly adapting Pulmonary Stretch Receptors (SARs) located below the carina in response to right atrial injections of histamine (60 and 80 μg/kg) in anesthetized artificially ventilated rabbits with bilateral vagotomy. After histamine was injected into the right atrium, the SARs became more active during expiration but decreased their activity during inspiration. These changes were more pronounced by increasing the dosage of histamine. However, administration of histamine had no significant effect on tracheal pressure (P_T). Verapamil treatment (1 mg/kg) did not alter the SAR response to histamine, whereas the responses of SARs to histamine at different dosages were significantly diminished by treatment with nifedipine (1 mg/kg). Mequitazine (1 mg/kg), a potent H_1-receptor blocker, blocked completely all the responses of SAR activity to histamine. These results suggest that the effect of histamine 60–80 μg/kg on SAR activity is mediated by the activation of H_1-Receptors of the peripheral airway smooth muscle and that this activation, at least in part, involves the opening of calcium channels of the airway smooth muscle.
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effect of ouabain on the afterhyperpolarization of slowly adapting Pulmonary Stretch Receptors in the rat lung
Brain Research, 2006Co-Authors: Shigeji Matsumoto, Chikako Saiki, Mamoru Takeda, Shinki Yoshida, Yumi KumagaiAbstract:Abstract In anesthetized, artificially ventilated rats with one vagus nerve section, the purposes of the present study were to investigate whether release from phasic consecutive hyperinflations (inflation volume = 3 tidal volumes) results in the afterhyperpolarization (AHP) of the slowly adapting Pulmonary Stretch receptor (SAR) activity and whether the effect of ouabain, a Na+–K+ ATPase inhibitor, alters AHP of the SAR activity seen after release from maintained inflations. Release from 10 consecutive phasic hyperinflations did not cause any significant inhibition of SAR activity. Release from maintained inflations (for approximately 10 and 15 cmH2O) for 5 s produced the induction of disappearance of SAR activity, corresponding with the AHP. Intravenous administration of ouabain (20 and 40 μg/kg) had no significant effects on the responses of SAR activity and SAR adaptation index (AI) to maintained inflations, but ouabain treatment with at 40 μg/kg resulted in a significant increase in the SAR activity after stopping the respirator and significantly attenuated the AHP of the SAR activity. In the immunohistochemical study, we found Na+–K+ ATPase α3-subunit-isoforms-like immunoreactivity in SAR terminals, forming leaflike extensions in the intraPulmonary bronchioles at different diameters, and those terminals were buried in the smooth muscle. In the same sections, the α1 subunit immunoreactivity of SAR terminals was not found. These results suggest that the mechanism of generating the AHP of SARs is mainly mediated by the activation of Na+–K+ ATPase α3 subunit isoform.
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the inhibitory effect of ouabain on the response of slowly adapting Pulmonary Stretch Receptors to hyperinflation in the rabbit
Life Sciences, 2005Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Yasuo Itoh, Yoshinobu Fujimi, Mamoru TakedaAbstract:Abstract The combined effects of ouabain (Na + –K + ATPase inhibitor) and hyperinflation (inflation volume = three tidal volumes) on slowly adapting Pulmonary Stretch Receptors (SARs) were studied before and after administration of nifedipine (an L-type Ca 2+ channel blocker) and KB-R7943 (a reverse-mode Na + –Ca 2+ exchanger blocker) in anesthetized, artificially ventilated rabbits after bilateral vagotomy. Before ouabain administration, hyperinflation stimulated SAR activity. After 20 min of ouabain administration (30 μg/kg) the SARs increased discharge rates in normal inflation. Under these conditions, hyperinflation initially stimulated SAR activity but subsequently inhibited the activity at peak inflation. Additional administration of 60 μg/kg ouabain (total dose = 90 μg/kg) caused a further stimulation of SAR activity, but 20 min later both normal inflation and hyperinflation resulted in a greater inhibition of the receptor activity. The hyperinflation-induced SAR inhibition in the presence of ouabain (30 μg/kg) was not significantly altered by administration of either nifedipine (2 and 4 mg/kg) or KB-R7943 (1 and 3 mg/kg). In another series of experiments, we further examined the combined effects of ouabain and hyperinflation in veratridine (a Na + channel opener, 40 μg/kg)-treated animals. After recovery from the veratridine effect on SAR activity, which vigorously stimulated the receptor activity, ouabain treatment (30 μg/kg) that silenced the receptor activity at peak inflation greatly inhibited hyperinflation-induced SAR stimulation. These results suggest that hyperinflation-induced SAR inhibition in the presence of ouabain may be related to a Na + overload, but not to a Ca 2+ influx via activation of L-type Ca 2+ channels, in the SAR endings.
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effects of acetazolamide and 4 aminoprydine on the responses of deflationary slowly adapting Pulmonary Stretch Receptors to co2 inhalation in the rat
Life Sciences, 2003Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Jun Kadoi, Mamoru TakedaAbstract:Abstract The inhibitory effect of CO 2 on deflationary slowly adapting Pulmonary Stretch Receptors (deflationary SARs) was investigated before and after administration of acetazolamide, a carbonic anhydrase (CA) inhibitor, or 4-aminopyridine (4-AP), a K + channel blocker, in anesthetized, artificially ventilated rats after unilateral vagotomy. CO 2 inhalation (maximum tracheal CO 2 concentration ranging from 9 to 12%) for approximately 60 s decreased the impulse activity of deflationary SARs but had no significant effect on tracheal pressure (P T ) as an index of bronchomotor tone. Acetazolamide treatment (20 mg/kg) diminished the inhibitory response of deflationary SARs to CO 2 inhalation. 4-AP (0.7 and 2.0 mg/kg) dose-dependently attenuated the decrease in deflationary SAR activity induced by CO 2 inhalation. When comparing the maximum attenuation due to 4-AP (2.0 mg/kg) and acetazolamide (20 mg/kg) in CO 2 -induced deflationary SAR inhibition, blockade of K + channels had a more pronounced effect. These results suggest that inhibition of deflationary SARs by CO 2 inhalation may be largely mediated by the stimulating action of 4-AP-sensitive K + currents in the nerve terminals of the Receptors.
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excitatory mechanism of deflationary slowly adapting Pulmonary Stretch Receptors in the rat lung
Journal of Pharmacology and Experimental Therapeutics, 2002Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The excitatory responses of deflationary slowly adapting Pulmonary Stretch receptor (SAR) activity to lung deflation ranging from approximately −15 to −25 cm of H 2 O for approximately 5 s were examined before and after administration of flecainide, a Na + channel blocker, and K + channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 μg/kg), an Na + channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other Receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na + channels on the nerve terminals of deflationary SARs.
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effects of potassium channel and na ca2 exchange blockers on the responses of slowly adapting Pulmonary Stretch Receptors to hyperinflation in flecainide treated rats
British Journal of Pharmacology, 2001Co-Authors: Shigeji Matsumoto, Takeshi Tanimoto, Chikako Saiki, Mizuho Ikeda, Toshimi Nishikawa, Shinki Yoshida, Mamoru TakedaAbstract:The effects of K+ channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na+ – Ca2+ exchange blocker, 2-[2-[4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), on the responses of slowly adapting Pulmonary Stretch receptor activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anaesthetized, artificially ventilated, unilaterally vagotomized rats after pretreatment with a Na+ channel blocker flecainide. The administration of flecainide (9 mg kg−1) at a dose greater than that which abolished 50 μg kg−1 veratridine-induced SAR stimulation also inhibited hyperinflation-induced stimulation of SARs. In flecainide-treated animals, administration of 4-AP (0.7 and 2 mg kg−1) stimulated SAR activity during normal inflation and also caused a partial blockade of hyperinflation-induced SAR inhibition. The discharges of SARs during normal inflation in flecainide-treated animals were not significantly altered by administration of either TEA (2 and 7 mg kg−1) or KB-R7943 (1 and 3 mg kg−1), but both K+ channel and Na+-Ca2+ exchange blockers partially attenuated hyperinflation-induced SAR inhibition. These results suggest that hyperinflation-induced SAR inhibition in the presence of flecainide (9 mg kg−1) involves the activation of several K+ conductance pathways. British Journal of Pharmacology (2001) 134, 682–690; doi:10.1038/sj.bjp.0704277
