The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform

Herman Meurs - One of the best experts on this subject based on the ideXlab platform.

  • arginase attenuates inhibitory Nonadrenergic Noncholinergic Nerve induced nitric oxide generation and airway smooth muscle relaxation
    Respiratory Research, 2005
    Co-Authors: Harm Maarsingh, Johan Zaagsma, Herman Meurs
    Abstract:

    Background: Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO) production, presumably by competition with epithelial constitutive NO synthase for the common substrate, Larginine. Using guinea pig tracheal open-ring preparations, we now investigated the involvement of arginase in the modulation of neuronal nitric oxide synthase (nNOS)-mediated relaxation induced by inhibitory Nonadrenergic Noncholinergic (iNANC) Nerve stimulation. Methods: Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz)-induced relaxation was measured in tracheal preparations precontracted to 30% with histamine, in the presence of 1 µM atropine and 3 µM indomethacin. The contribution of NO to the EFS-induced relaxation was assessed by the nonselective NOS inhibitor L-NNA (0.1 mM), while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor nor-NOHA (10 µM). Furthermore, the role of substrate availability to nNOS in EFS-induced relaxation was measured in the presence of various concentrations of exogenous L-arginine. Results: EFS induced a frequency-dependent relaxation, ranging from 6.6 ± 0.8% at 0.5 Hz to 74.6 ± 1.2% at 16 Hz, which was inhibited with the NOS inhibitor L-NNA by 78.0 ± 10.5% at 0.5 Hz to 26.7 ± 7.7% at 8 Hz (P < 0.01 all). In contrast, the arginase inhibitor nor-NOHA increased EFSinduced relaxation by 3.3 ± 1.2-fold at 0.5 Hz to 1.2 ± 0.1-fold at 4 Hz (P < 0.05 all), which was reversed by L-NNA to the level of control airways in the presence of L-NNA (P < 0.01 all). Similar to nor-NOHA, exogenous L-arginine increased EFS-induced airway relaxation (P < 0.05 all). Conclusion: The results indicate that endogenous arginase activity attenuates iNANC Nervemediated airway relaxation by inhibition of NO generation, presumably by limiting L-arginine availability to nNOS.

Harm Maarsingh - One of the best experts on this subject based on the ideXlab platform.

  • arginase attenuates inhibitory Nonadrenergic Noncholinergic Nerve induced nitric oxide generation and airway smooth muscle relaxation
    Respiratory Research, 2005
    Co-Authors: Harm Maarsingh, Johan Zaagsma, Herman Meurs
    Abstract:

    Background: Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO) production, presumably by competition with epithelial constitutive NO synthase for the common substrate, Larginine. Using guinea pig tracheal open-ring preparations, we now investigated the involvement of arginase in the modulation of neuronal nitric oxide synthase (nNOS)-mediated relaxation induced by inhibitory Nonadrenergic Noncholinergic (iNANC) Nerve stimulation. Methods: Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz)-induced relaxation was measured in tracheal preparations precontracted to 30% with histamine, in the presence of 1 µM atropine and 3 µM indomethacin. The contribution of NO to the EFS-induced relaxation was assessed by the nonselective NOS inhibitor L-NNA (0.1 mM), while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor nor-NOHA (10 µM). Furthermore, the role of substrate availability to nNOS in EFS-induced relaxation was measured in the presence of various concentrations of exogenous L-arginine. Results: EFS induced a frequency-dependent relaxation, ranging from 6.6 ± 0.8% at 0.5 Hz to 74.6 ± 1.2% at 16 Hz, which was inhibited with the NOS inhibitor L-NNA by 78.0 ± 10.5% at 0.5 Hz to 26.7 ± 7.7% at 8 Hz (P < 0.01 all). In contrast, the arginase inhibitor nor-NOHA increased EFSinduced relaxation by 3.3 ± 1.2-fold at 0.5 Hz to 1.2 ± 0.1-fold at 4 Hz (P < 0.05 all), which was reversed by L-NNA to the level of control airways in the presence of L-NNA (P < 0.01 all). Similar to nor-NOHA, exogenous L-arginine increased EFS-induced airway relaxation (P < 0.05 all). Conclusion: The results indicate that endogenous arginase activity attenuates iNANC Nervemediated airway relaxation by inhibition of NO generation, presumably by limiting L-arginine availability to nNOS.

Johan Zaagsma - One of the best experts on this subject based on the ideXlab platform.

  • arginase attenuates inhibitory Nonadrenergic Noncholinergic Nerve induced nitric oxide generation and airway smooth muscle relaxation
    Respiratory Research, 2005
    Co-Authors: Harm Maarsingh, Johan Zaagsma, Herman Meurs
    Abstract:

    Background: Recent evidence suggests that endogenous arginase activity potentiates airway responsiveness to methacholine by attenuation of agonist-induced nitric oxide (NO) production, presumably by competition with epithelial constitutive NO synthase for the common substrate, Larginine. Using guinea pig tracheal open-ring preparations, we now investigated the involvement of arginase in the modulation of neuronal nitric oxide synthase (nNOS)-mediated relaxation induced by inhibitory Nonadrenergic Noncholinergic (iNANC) Nerve stimulation. Methods: Electrical field stimulation (EFS; 150 mA, 4 ms, 4 s, 0.5 – 16 Hz)-induced relaxation was measured in tracheal preparations precontracted to 30% with histamine, in the presence of 1 µM atropine and 3 µM indomethacin. The contribution of NO to the EFS-induced relaxation was assessed by the nonselective NOS inhibitor L-NNA (0.1 mM), while the involvement of arginase activity in the regulation of EFS-induced NO production and relaxation was investigated by the effect of the specific arginase inhibitor nor-NOHA (10 µM). Furthermore, the role of substrate availability to nNOS in EFS-induced relaxation was measured in the presence of various concentrations of exogenous L-arginine. Results: EFS induced a frequency-dependent relaxation, ranging from 6.6 ± 0.8% at 0.5 Hz to 74.6 ± 1.2% at 16 Hz, which was inhibited with the NOS inhibitor L-NNA by 78.0 ± 10.5% at 0.5 Hz to 26.7 ± 7.7% at 8 Hz (P < 0.01 all). In contrast, the arginase inhibitor nor-NOHA increased EFSinduced relaxation by 3.3 ± 1.2-fold at 0.5 Hz to 1.2 ± 0.1-fold at 4 Hz (P < 0.05 all), which was reversed by L-NNA to the level of control airways in the presence of L-NNA (P < 0.01 all). Similar to nor-NOHA, exogenous L-arginine increased EFS-induced airway relaxation (P < 0.05 all). Conclusion: The results indicate that endogenous arginase activity attenuates iNANC Nervemediated airway relaxation by inhibition of NO generation, presumably by limiting L-arginine availability to nNOS.

Satish Rattan - One of the best experts on this subject based on the ideXlab platform.

  • inhibitory neurotransmission in lethal spotted mutant mice a model for hirschsprung s disease
    Gastroenterology, 1997
    Co-Authors: Sushanta Chakder, Kirk M Mchugh, Satish Rattan
    Abstract:

    Abstract BACKGROUND & AIMS: The pathogenesis of Hirschsprung's disease is not well understood. The suitability of the animal model for the unknown pathogenesis of inhibitory neurotransmission in Hirschsprung's disease was investigated. METHODS: Circular smooth muscle strips from the internal anal sphincter (IAS) and distal colon (2, 6, 8, 16, and 24 mm from the anal verge) from normal and Ls/Ls mice (mice homozygous for the lethal spotting mutation that develop fetal megacolon after aganglionosis of the terminal colon) were prepared to record changes in isometric tensions in response to different agents and Nonadrenergic, Noncholinergic Nerve stimulation by electrical field stimulation. RESULTS: Bethanechol was used to produce contraction of the smooth muscle strips of distal colon to record a decrease in the tension. Conversely, the IAS smooth muscle strips developed spontaneous tone. In the normal homozygous mice, electrical field stimulation caused a biphasic response, an initial decrease followed by an after- contraction, whereas in Ls/Ls mice, the predominant response was contraction. All smooth muscle strips from normal and Ls/Ls mice produced relaxation in response to sodium nitroprusside and vasoactive intestinal polypeptide. CONCLUSIONS: Ls/Ls mice may serve as an appropriate animal model to investigate the pathogenesis of the inhibitory neurotransmission in Hirschsprung's disease in the distal colon and IAS. (Gastroenterology 1997 May;112(5):1575-85)

  • nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter
    Gastroenterology, 1992
    Co-Authors: Satish Rattan, Anjan Sarkar, Sushanta Chakder
    Abstract:

    Abstract The role of nitric oxide in relaxation of the internal anal sphincter (IAS) in response to the rectoanal reflex was studied in the opossum. Resting pressures in the IAS (IASP) were monitored using low-compliance continuously perfused catheters. The NO-synthase inhibitor l- N G -nitro-arginine (l-NNA) caused significant and dose-dependent suppression of the decrease in IASP in response to the reflex mimicked by the rectal balloon distention. NO-synthase inhibitor blocked IAS relaxation in response not only to rectoanal reflex but also to other neural stimuli such as sacral Nerve stimulation, local intramural stimulation, and the nicotinic ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium. Suppression of the neurally mediated IAS relaxation by l-NNA was stereoselective; d-NNA had no effect on the relaxation. The suppression of the rectoanal reflex-induced IAS relaxation by l-NNA was completely reversed by NO precursor l-arginine stereoselectively as d-arginine failed to reverse the suppressed IAS relaxation. Sodium nitroprusside caused a decrease in IASP that was modified neither by the neurotoxin tetrodotoxin nor by l-NNA. Furthermore, the decrease in IASP by the direct-acting β-adrenoceptor agonist isoproterenol was also not modified by the inhibitor of NO synthase. It is concluded that NO or an NO-like substance is an important mediator of IAS relaxation in response to Nonadrenergic, Noncholinergic Nerve stimulation.

Sushanta Chakder - One of the best experts on this subject based on the ideXlab platform.

  • inhibitory neurotransmission in lethal spotted mutant mice a model for hirschsprung s disease
    Gastroenterology, 1997
    Co-Authors: Sushanta Chakder, Kirk M Mchugh, Satish Rattan
    Abstract:

    Abstract BACKGROUND & AIMS: The pathogenesis of Hirschsprung's disease is not well understood. The suitability of the animal model for the unknown pathogenesis of inhibitory neurotransmission in Hirschsprung's disease was investigated. METHODS: Circular smooth muscle strips from the internal anal sphincter (IAS) and distal colon (2, 6, 8, 16, and 24 mm from the anal verge) from normal and Ls/Ls mice (mice homozygous for the lethal spotting mutation that develop fetal megacolon after aganglionosis of the terminal colon) were prepared to record changes in isometric tensions in response to different agents and Nonadrenergic, Noncholinergic Nerve stimulation by electrical field stimulation. RESULTS: Bethanechol was used to produce contraction of the smooth muscle strips of distal colon to record a decrease in the tension. Conversely, the IAS smooth muscle strips developed spontaneous tone. In the normal homozygous mice, electrical field stimulation caused a biphasic response, an initial decrease followed by an after- contraction, whereas in Ls/Ls mice, the predominant response was contraction. All smooth muscle strips from normal and Ls/Ls mice produced relaxation in response to sodium nitroprusside and vasoactive intestinal polypeptide. CONCLUSIONS: Ls/Ls mice may serve as an appropriate animal model to investigate the pathogenesis of the inhibitory neurotransmission in Hirschsprung's disease in the distal colon and IAS. (Gastroenterology 1997 May;112(5):1575-85)

  • nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter
    Gastroenterology, 1992
    Co-Authors: Satish Rattan, Anjan Sarkar, Sushanta Chakder
    Abstract:

    Abstract The role of nitric oxide in relaxation of the internal anal sphincter (IAS) in response to the rectoanal reflex was studied in the opossum. Resting pressures in the IAS (IASP) were monitored using low-compliance continuously perfused catheters. The NO-synthase inhibitor l- N G -nitro-arginine (l-NNA) caused significant and dose-dependent suppression of the decrease in IASP in response to the reflex mimicked by the rectal balloon distention. NO-synthase inhibitor blocked IAS relaxation in response not only to rectoanal reflex but also to other neural stimuli such as sacral Nerve stimulation, local intramural stimulation, and the nicotinic ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium. Suppression of the neurally mediated IAS relaxation by l-NNA was stereoselective; d-NNA had no effect on the relaxation. The suppression of the rectoanal reflex-induced IAS relaxation by l-NNA was completely reversed by NO precursor l-arginine stereoselectively as d-arginine failed to reverse the suppressed IAS relaxation. Sodium nitroprusside caused a decrease in IASP that was modified neither by the neurotoxin tetrodotoxin nor by l-NNA. Furthermore, the decrease in IASP by the direct-acting β-adrenoceptor agonist isoproterenol was also not modified by the inhibitor of NO synthase. It is concluded that NO or an NO-like substance is an important mediator of IAS relaxation in response to Nonadrenergic, Noncholinergic Nerve stimulation.