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Shigetoshi Chiba - One of the best experts on this subject based on the ideXlab platform.
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Inotropic, chronotropic, and Dromotropic effects mediated via parasympathetic ganglia in the dog heart
American journal of physiology. Heart and circulatory physiology, 2000Co-Authors: Masato Tsuboi, Yasuyuki Furukawa, Fumio Kurogouchi, Koichi Nakajima, Shigetoshi ChibaAbstract:Some parasympathetic ganglionic cells are located in the epicardial fat pad between the medial superior vena cava and the aortic root (SVC-Ao fat pad) of the dog. We investigated whether the ganglionic cells in the SVC-Ao fat pad control the right atrial contractile force, sinus cycle length (SCL), and atrioventricular (AV) conduction in the autonomically decentralized heart of the anesthetized dog. Stimulation of both sides of the cervical vagal complexes (CVS) decreased right atrial contractile force, increased SCL, and prolonged AV interval. Stimulation of the rate-related parasympathetic nerves to the sinoatrial (SA) node (SAPS) increased SCL and decreased atrial contractile force. Stimulation of the AV conduction-related parasympathetic nerves to the AV node prolonged AV interval. Trimethaphan, a ganglionic nicotinic receptor blocker, injected into the SVC-Ao fat pad attenuated the negative inotropic, chronotropic, and Dromotropic responses to CVS by 33 approximately 37%. On the other hand, lidocaine, a sodium channel blocker, injected into the SVC-Ao fat pad almost totally inhibited the inotropic and chronotropic responses to CVS and partly inhibited the Dromotropic one. Lidocaine or trimethaphan injected into the SAPS locus abolished the inotropic responses to SAPS, but it partly attenuated those to CVS, although these treatments abolished the chronotropic responses to SAPS or CVS. These results suggest that parasympathetic ganglionic cells in the SVC-Ao fat pad, differing from those in SA and AV fat pads, nonselectively control the atrial contractile force, SCL, and AV conduction partially in the dog heart.
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CNP causes receptor-mediated positive Dromotropic effects in anesthetized dog hearts
The American journal of physiology, 1998Co-Authors: Masamichi Hirose, Yasuyuki Furukawa, Yusuke Miyashita, Fumio Kurogouchi, Koichi Nakajima, Masato Tsuboi, Shigetoshi ChibaAbstract:No data are available for the direct effect of C-type natriuretic peptide (CNP) on atrioventricular (AV) conduction in mammalian hearts. Thus we studied the Dromotropic effects of CNP-22 injected into the AV node artery in autonomically decentralized hearts in open-chest, anesthetized dogs. CNP decreased AV interval (AV conduction time) in a dose-dependent manner with increase in coronary artery blood flow rate in six anesthetized dogs. Isosorbide dinitrate did not affect AV interval, but it increased coronary artery blood flow rate. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142–1, inhibited the decreases in AV interval and the increases in coronary blood flow rate in response to CNP, whereas propranolol did not affect the positive Dromotropic response to CNP. These results demonstrate that CNP decreases AV interval and increases coronary artery blood flow rate mediated by a guanylyl cyclase-linked natriuretic peptide receptor, but not β-adrenoceptor, in the dog heart.
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PACAP-27 causes negative and positive Dromotropic effects in anesthetized dogs
European journal of pharmacology, 1997Co-Authors: Masamichi Hirose, Yasuyuki Furukawa, Yoshito Nagashima, Manoj Lakhe, Yusuke Miyashita, Shigetoshi ChibaAbstract:While pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified radioimmunologically in the rat heart, the physiological role of PACAP has not been elucidated in the regulation of the atrioventricular conduction in the heart. We, therefore, determined the Dromotropic effects of PACAP-27 injected into the cannulated atrioventricular node artery in the autonomically decentralized heart of the open-chest, anesthetized dog. PACAP-27 caused transient positive followed by negative Dromotropic responses in a dose-dependent manner, whereas vasoactive intestinal peptide (VIP) caused only a positive Dromotropic response. Atropine and tetrodotoxin blocked the negative Dromotropic response to PACAP-27 and after blockade PACAP-27 caused only a positive Dromotropic response. Tetrodotoxin and propranolol did not affect the positive Dromotropic response to PACAP-27 in atropine-treated dogs. PACAP-27 altered the atrio-His bundle interval but did not alter the His-ventricle interval. These results demonstrate that PACAP-27 prolongs the atrio-His bundle interval due to the liberation of acetylcholine from parasympathetic nerves and decreases it by a non-adrenergic mechanism in the dog heart in situ.
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Different sympathetic–parasympathetic interactions on sinus rate and AV conduction in dog hearts
European Journal of Pharmacology, 1997Co-Authors: Yasuyuki Furukawa, Masahiro Narita, Manabu Takei, Yasuyuki Karasawa, Akihiro Tada, Hiroshi Zenda, Shigetoshi ChibaAbstract:We investigated the sympathetic-parasympathetic interactions involved in SA nodal pacemaker activity and AV conductivity in the anesthetized dog heart. Stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAPS) and stimulation of the intracardiac parasympathetic nerves to the AV nodal region (AVPS) induced negative chronotropic and Dromotropic responses, respectively. Cardiac sympathetic stimulation, aminophylline, 3-isobutyl-1-methylxanthine (IBMX, a relatively pure nonselective phosphodiesterase inhibitor) and methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-p iridine-5-carboxylate (Bay k 8644, a Ca2+ channel agonist) increased sinus rate and decreased AV conduction time. Sympathetic stimulation augmented the negative chronotropic response to SAPS but not the negative Dromotropic response to AVPS, IBMX augmented both responses, Bay k 8644 augmented the chronotropic response and attenuated the Dromotropic response, and aminophylline did not affect the chronotropic response to SAPS and inhibited the Dromotropic response to AVPS. Additionally, when Bay k 8644 directly given via the AV node artery decreased AV conduction time, it attenuated the negative Dromotropic response to AVPS and carbachol injected into the AV node artery. These results suggest that the differential sympathetic-parasympathetic interactions on sinus rate and AV conduction are at least partly induced by an interaction between changes in slow inward Ca2+ current or intracellular Ca2+ and the cardiac effects of acetylcholine in the heart in situ.
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Atrioventricular junctional rhythm induced by sympathetic stimulation in E-4031-treated dog hearts.
Journal of Cardiovascular Pharmacology, 1996Co-Authors: Hiroshi Imamura, Miho Kasama, Yuji Hoyano, Yasuyuki Furukawa, Hirofumi Nakano, Kyohei Yamazaki, Shigetoshi ChibaAbstract:To investigate the role of delayed rectifier potassium current (I K ) on the sympathetic control of the heart, we studied the effects of E-403 1, a blocker of the rapidly activating type of I K (I Kr ), on the chronotropic, Dromotropic, and inotropic responses to sympathetic nerve stimulation in the autonomically decentralized hearts of open-chest anesthetized dogs. E-4031 (0.01-3 μmol/kg intravenously, i.v.) decreased the heart rate (HR) dose dependently without affecting other cardiac functions. After E-4031 treatment, cardiac sympathetic nerve stimulation changed the sinus rhythm to the atrioventricular (AV) junctional rhythm in 6 of 11 anesthetized dogs (55%). In three of six junctional rhythm hearts, sinus rhythm supervened during sympathetic stimulation for 2 min. The number of pacemaker shifts to junctional rhythm increased as the dose of E-4031 was increased. However, E-4031 attenuated neither the positive chronotropic, Dromotropic, nor right atrial and ventricular inotropic responses to sympathetic nerve stimulation. These results suggest that I Kr inhibition may induce the AV junctional rhythm due to the combination of the different participation of I Kr , the different resting potentials, and the different sensitivity to sympathetic activation among cardiac pacemaker cells.
Yasuyuki Furukawa - One of the best experts on this subject based on the ideXlab platform.
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Inotropic, chronotropic, and Dromotropic effects mediated via parasympathetic ganglia in the dog heart
American journal of physiology. Heart and circulatory physiology, 2000Co-Authors: Masato Tsuboi, Yasuyuki Furukawa, Fumio Kurogouchi, Koichi Nakajima, Shigetoshi ChibaAbstract:Some parasympathetic ganglionic cells are located in the epicardial fat pad between the medial superior vena cava and the aortic root (SVC-Ao fat pad) of the dog. We investigated whether the ganglionic cells in the SVC-Ao fat pad control the right atrial contractile force, sinus cycle length (SCL), and atrioventricular (AV) conduction in the autonomically decentralized heart of the anesthetized dog. Stimulation of both sides of the cervical vagal complexes (CVS) decreased right atrial contractile force, increased SCL, and prolonged AV interval. Stimulation of the rate-related parasympathetic nerves to the sinoatrial (SA) node (SAPS) increased SCL and decreased atrial contractile force. Stimulation of the AV conduction-related parasympathetic nerves to the AV node prolonged AV interval. Trimethaphan, a ganglionic nicotinic receptor blocker, injected into the SVC-Ao fat pad attenuated the negative inotropic, chronotropic, and Dromotropic responses to CVS by 33 approximately 37%. On the other hand, lidocaine, a sodium channel blocker, injected into the SVC-Ao fat pad almost totally inhibited the inotropic and chronotropic responses to CVS and partly inhibited the Dromotropic one. Lidocaine or trimethaphan injected into the SAPS locus abolished the inotropic responses to SAPS, but it partly attenuated those to CVS, although these treatments abolished the chronotropic responses to SAPS or CVS. These results suggest that parasympathetic ganglionic cells in the SVC-Ao fat pad, differing from those in SA and AV fat pads, nonselectively control the atrial contractile force, SCL, and AV conduction partially in the dog heart.
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CNP causes receptor-mediated positive Dromotropic effects in anesthetized dog hearts
The American journal of physiology, 1998Co-Authors: Masamichi Hirose, Yasuyuki Furukawa, Yusuke Miyashita, Fumio Kurogouchi, Koichi Nakajima, Masato Tsuboi, Shigetoshi ChibaAbstract:No data are available for the direct effect of C-type natriuretic peptide (CNP) on atrioventricular (AV) conduction in mammalian hearts. Thus we studied the Dromotropic effects of CNP-22 injected into the AV node artery in autonomically decentralized hearts in open-chest, anesthetized dogs. CNP decreased AV interval (AV conduction time) in a dose-dependent manner with increase in coronary artery blood flow rate in six anesthetized dogs. Isosorbide dinitrate did not affect AV interval, but it increased coronary artery blood flow rate. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142–1, inhibited the decreases in AV interval and the increases in coronary blood flow rate in response to CNP, whereas propranolol did not affect the positive Dromotropic response to CNP. These results demonstrate that CNP decreases AV interval and increases coronary artery blood flow rate mediated by a guanylyl cyclase-linked natriuretic peptide receptor, but not β-adrenoceptor, in the dog heart.
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PACAP-27 causes negative and positive Dromotropic effects in anesthetized dogs
European journal of pharmacology, 1997Co-Authors: Masamichi Hirose, Yasuyuki Furukawa, Yoshito Nagashima, Manoj Lakhe, Yusuke Miyashita, Shigetoshi ChibaAbstract:While pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified radioimmunologically in the rat heart, the physiological role of PACAP has not been elucidated in the regulation of the atrioventricular conduction in the heart. We, therefore, determined the Dromotropic effects of PACAP-27 injected into the cannulated atrioventricular node artery in the autonomically decentralized heart of the open-chest, anesthetized dog. PACAP-27 caused transient positive followed by negative Dromotropic responses in a dose-dependent manner, whereas vasoactive intestinal peptide (VIP) caused only a positive Dromotropic response. Atropine and tetrodotoxin blocked the negative Dromotropic response to PACAP-27 and after blockade PACAP-27 caused only a positive Dromotropic response. Tetrodotoxin and propranolol did not affect the positive Dromotropic response to PACAP-27 in atropine-treated dogs. PACAP-27 altered the atrio-His bundle interval but did not alter the His-ventricle interval. These results demonstrate that PACAP-27 prolongs the atrio-His bundle interval due to the liberation of acetylcholine from parasympathetic nerves and decreases it by a non-adrenergic mechanism in the dog heart in situ.
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Different sympathetic–parasympathetic interactions on sinus rate and AV conduction in dog hearts
European Journal of Pharmacology, 1997Co-Authors: Yasuyuki Furukawa, Masahiro Narita, Manabu Takei, Yasuyuki Karasawa, Akihiro Tada, Hiroshi Zenda, Shigetoshi ChibaAbstract:We investigated the sympathetic-parasympathetic interactions involved in SA nodal pacemaker activity and AV conductivity in the anesthetized dog heart. Stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAPS) and stimulation of the intracardiac parasympathetic nerves to the AV nodal region (AVPS) induced negative chronotropic and Dromotropic responses, respectively. Cardiac sympathetic stimulation, aminophylline, 3-isobutyl-1-methylxanthine (IBMX, a relatively pure nonselective phosphodiesterase inhibitor) and methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-p iridine-5-carboxylate (Bay k 8644, a Ca2+ channel agonist) increased sinus rate and decreased AV conduction time. Sympathetic stimulation augmented the negative chronotropic response to SAPS but not the negative Dromotropic response to AVPS, IBMX augmented both responses, Bay k 8644 augmented the chronotropic response and attenuated the Dromotropic response, and aminophylline did not affect the chronotropic response to SAPS and inhibited the Dromotropic response to AVPS. Additionally, when Bay k 8644 directly given via the AV node artery decreased AV conduction time, it attenuated the negative Dromotropic response to AVPS and carbachol injected into the AV node artery. These results suggest that the differential sympathetic-parasympathetic interactions on sinus rate and AV conduction are at least partly induced by an interaction between changes in slow inward Ca2+ current or intracellular Ca2+ and the cardiac effects of acetylcholine in the heart in situ.
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Atrioventricular junctional rhythm induced by sympathetic stimulation in E-4031-treated dog hearts.
Journal of Cardiovascular Pharmacology, 1996Co-Authors: Hiroshi Imamura, Miho Kasama, Yuji Hoyano, Yasuyuki Furukawa, Hirofumi Nakano, Kyohei Yamazaki, Shigetoshi ChibaAbstract:To investigate the role of delayed rectifier potassium current (I K ) on the sympathetic control of the heart, we studied the effects of E-403 1, a blocker of the rapidly activating type of I K (I Kr ), on the chronotropic, Dromotropic, and inotropic responses to sympathetic nerve stimulation in the autonomically decentralized hearts of open-chest anesthetized dogs. E-4031 (0.01-3 μmol/kg intravenously, i.v.) decreased the heart rate (HR) dose dependently without affecting other cardiac functions. After E-4031 treatment, cardiac sympathetic nerve stimulation changed the sinus rhythm to the atrioventricular (AV) junctional rhythm in 6 of 11 anesthetized dogs (55%). In three of six junctional rhythm hearts, sinus rhythm supervened during sympathetic stimulation for 2 min. The number of pacemaker shifts to junctional rhythm increased as the dose of E-4031 was increased. However, E-4031 attenuated neither the positive chronotropic, Dromotropic, nor right atrial and ventricular inotropic responses to sympathetic nerve stimulation. These results suggest that I Kr inhibition may induce the AV junctional rhythm due to the combination of the different participation of I Kr , the different resting potentials, and the different sensitivity to sympathetic activation among cardiac pacemaker cells.
Masahiro Narita - One of the best experts on this subject based on the ideXlab platform.
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Different sympathetic–parasympathetic interactions on sinus rate and AV conduction in dog hearts
European Journal of Pharmacology, 1997Co-Authors: Yasuyuki Furukawa, Masahiro Narita, Manabu Takei, Yasuyuki Karasawa, Akihiro Tada, Hiroshi Zenda, Shigetoshi ChibaAbstract:We investigated the sympathetic-parasympathetic interactions involved in SA nodal pacemaker activity and AV conductivity in the anesthetized dog heart. Stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAPS) and stimulation of the intracardiac parasympathetic nerves to the AV nodal region (AVPS) induced negative chronotropic and Dromotropic responses, respectively. Cardiac sympathetic stimulation, aminophylline, 3-isobutyl-1-methylxanthine (IBMX, a relatively pure nonselective phosphodiesterase inhibitor) and methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-p iridine-5-carboxylate (Bay k 8644, a Ca2+ channel agonist) increased sinus rate and decreased AV conduction time. Sympathetic stimulation augmented the negative chronotropic response to SAPS but not the negative Dromotropic response to AVPS, IBMX augmented both responses, Bay k 8644 augmented the chronotropic response and attenuated the Dromotropic response, and aminophylline did not affect the chronotropic response to SAPS and inhibited the Dromotropic response to AVPS. Additionally, when Bay k 8644 directly given via the AV node artery decreased AV conduction time, it attenuated the negative Dromotropic response to AVPS and carbachol injected into the AV node artery. These results suggest that the differential sympathetic-parasympathetic interactions on sinus rate and AV conduction are at least partly induced by an interaction between changes in slow inward Ca2+ current or intracellular Ca2+ and the cardiac effects of acetylcholine in the heart in situ.
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Sympathetic Nerve Stimulation Activates Both β1- and β2-Adrenoceptors of SA and AV Nodes in Anesthetized Dog Hearts
Japanese journal of pharmacology, 1992Co-Authors: Manabu Takei, Yasuyuki Furukawa, Masahiro Narita, M. Murakami, Lei-ming Ren, Yasuyuki Karasawa, Shigetoshi ChibaAbstract:We investigated blocking effects of the selective β1-adrenoceptor blocker atenolol (0.1-100 μg/kg, i.v.), the selective β2-adrenoceptor blocker ICI 118, 551 (1-1000 μg/kg, i.v.) and the combination of the two drugs on positive chronotropic and Dromotropic responses to norepinephrine (NE) released by stimulation of the sympathetic nerves in anesthetized, neurally decentralized, open-chest dogs after atropine was given. Stimulation of the intracardiac sympathetic nerves to the SA nodal region or to the AV nodal region selectively increased heart rate or decreased AV conduction time, respectively. ICI 118, 551 inhibited the chronotropic or Dromotropic response to each stimulation in a dose-dependent manner, but its inhibition of the Dromotropic response was less than that of the chronotropic response. Atenolol similarly inhibited either the positive chronotropic or Dromotropic response to each stimulation in a dose-related manner. The combination of atenolol and ICI 118, 551 attenuated the responses to each stimulation more than atenolol alone. These data indicate that sympathetic nerve stimulation activates both β1- and β2-adrenoceptors of the SA and AV nodes and that the proportion of β2-adrenoceptor-mediated effects on the AV node is less than that on the SA node. These results suggest that neurally released NE in part controls physiological functional cardiac responses mediated through β2-adrenoceptors, in addition to the responses predominantly mediated through β1-adrenoceptors.
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Parasympatholytic effects of vecuronium are mediated by nicotinic and muscarinic receptors in hearts of anesthetized dogs.
The Journal of pharmacology and experimental therapeutics, 1992Co-Authors: Masahiro Narita, Yasuyuki Furukawa, M. Takei, M. Murakami, Lei-ming Ren, Shigetoshi ChibaAbstract:We investigated the blocking effects of vecuronium and pancuronium on the negative chronotropic and Dromotropic responses to stimulation of the parasympathetic nerves in the anesthetized, open-chest dog. We stimulated the intracardiac parasympathetic nerves to the SA nodal region (SAP stimulation) or to the atrioventricular nodal region (AVP stimulation). SAP stimulation or AVP stimulation selectively decreased heart rate or increased atrioventricular conduction time, respectively. Vecuronium and pancuronium inhibited the chronotropic response to SAP stimulation and the Dromotropic response to AVP stimulation in a dose-dependent manner. The ID50 of each drug for the Dromotropic response was less than that for the chronotropic response. The blocking effect of vecuronium on the negative cardiac responses to parasympathetic stimulation was about 10-fold less potent than that of pancuronium. These results suggest that the blocking effects of vecuronium and pancuronium on the negative chronotropic and Dromotropic responses to parasympathetic stimulation differ from those of atropine in the heart. In the isolated right atrium perfused with blood from the support dog, vecuronium, injected into the external jugular vein of the support dog, dose-dependently inhibited the negative chronotropic and inotropic responses to carbachol or SAP stimulation and the negative followed by positive chronotropic and inotropic responses to nicotine. The ID50 values for carbachol, nicotine and SAP stimulation were not significantly different. These results suggest that parasympatholytic effects of vecuronium are mediated by not only muscarinic receptors but also neuronal nicotinic receptors in hearts of anesthetized dogs.
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Functional participation in M1 receptor subtype on chronotropic and Dromotropic responses to vagus stimulation in anesthetized dogs.
The Journal of pharmacology and experimental therapeutics, 1991Co-Authors: Masahiro Narita, Yasuyuki Furukawa, M. Takei, M. Murakami, Lei-ming Ren, Y. Karasawa, Shigetoshi ChibaAbstract:We investigated blocking effects of pirenzepine, AF-DX 116 and atropine on the negative chronotropic and Dromotropic responses to stimulation of the intracardiac vagus nerves in the anesthetized, open-chest dogs. Stimulation of the intracardiac vagus nerves to the sinoatrial nodal region (stimulation of the intracardiac parasympathetic nerves to the sinoatrial nodal region) or to the atrioventricular nodal region (stimulation of intracardiac nerves to the atriventricular region) selectively decreased heart rate or increased atrioventricular conduction time, respectively. Pirenzepine at lower doses (0.3-3 microgram/kg i.v.) attenuated the stimulation of the negative chronotropic response to the intracardiac parasympathetic nerves to the sinoatrial nodal region to 80% of the control response significantly but did not affect the negative Dromotropic one. Similarly, higher doses (10-1000 micrograms/kg i.v.) of pirenzepine inhibited the chronotropic and Dromotropic responses to each stimulation in a dose-dependent manner. AF-DX 116 (0.3-300 microgram/kg i.v.) inhibited the chronotropic and Dromotropic responses to each stimulation in a similar dose-dependent manner. Atropine (1-30 microgram/kg i.v.) blocked the cardiac responses to each stimulation. However, the ID50 of atropine for the chronotropic response was less than that for the Dromotropic one, although ID50s of pirenzepine and AF-DX 116 for the chronotropic and Dromotropic responses were not different.(ABSTRACT TRUNCATED AT 250 WORDS)
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differential intracardiac sympathetic and parasympathetic innervation to the sa and av nodes in anesthetized dog hearts
Japanese Journal of Pharmacology, 1991Co-Authors: Yasuyuki Furukawa, Masahiro Narita, Manabu Takei, Osamu Kobayashi, Masayuki Haniuda, Shigetoshi ChibaAbstract:Abstract Stimulation of discrete intracardiac sympathetic nerves to the SA (SAS stimulation) or AV nodal region (AVS stimulation) increased the heart rate or decreased AV conduction time and caused an AV junctional rhythm, respectively, in anesthetized dogs treated with atropine. Topical application of tetrodotoxin (TTX) at the SAS or AVS stimulation locus totally inhibited the response to each stimulation, whereas each TTX treatment slightly attenuated the chronotropic response to the right ansa stimulation by 23 ± 7.7% and the Dromotropic response to the left ansa stimulation by 7 ± 7.5%. TTX abolished AVS stimulation-induced one. Before atropine, topical application of hexamethonium at the locus for stimulation of intracardiac parasympathetic nerves to the SA (SAP stimulation) or AV nodal region (AVP stimulation) abolished almost totally negative chronotropic responses to SAP and cervical vagus stimulation or negative Dromotropic responses to AVP and cervical vagus stimulation, respectively. These results demonstrate that activation of a very small population of intracardiac sympathetic nerves to target cells is enough to induce positive chronotropic and Dromotropic responses in the heart in situ, and that SA and AV nodal pacemaker activity and AV conductivity are controlled multi-directionally by intracardiac sympathetic nerves in contrast with parasympathetic ones.
Philip J. Gatti - One of the best experts on this subject based on the ideXlab platform.
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Ultrastructural circuitry of cardiorespiratory reflexes: there is a monosynaptic path between the nucleus of the solitary tract and vagal preganglionic motoneurons controlling atrioventricular conduction in the cat
Brain research, 1998Co-Authors: Karen J. Blinder, Philip J. Gatti, Tannis A. Johnson, Jean-marie Lauenstein, William P. Coleman, Alrich L. Gray, V. John MassariAbstract:We have tested the hypothesis: (1) that presumptive negative Dromotropic vagal preganglionic neurons in the ventrolateral nucleus ambiguus (NA-VL) can be selectively labelled from the heart, by injecting one of two fluorescent tracers into the two intracardiac ganglia which independently control sino-atrial (SA) rate or atrioventricular (AV) conduction; i.e., the SA and AV ganglia, respectively. The NA-VL was examined for the presence of single and/or double labelled cells. Over 91% of vagal preganglionic neurons in the NA-VL projecting to either intracardiac ganglion did not project to the second ganglion. Consequently, we also tested the hypothesis: (2) that there is a monosynaptic connection between neurons of the medial, and/or dorsolateral nucleus of the solitary tract (NTS), rostral to obex, and negative Dromotropic neurons in the NA-VL. An anterograde tracer was injected into the NTS, and a retrograde tracer into the AV ganglion. The anterograde marker was found in both myelinated and unmyelinated axons in the NA-VL, as well as in nerve terminals. Axo-somatic and axo-dendritic synapses were detected between terminals labelled from the NTS, and retrogradely labelled negative Dromotropic neurons in the NA-VL. This is the first ultrastructural demonstration of a monosynaptic pathway between neurons in the NTS and functionally associated (negative Dromotropic) cardioinhibitory neurons. The data are consistent with the hypothesis that the neuroanatomical circuitry mediating the vagal baroreflex control of AV conduction may be composed of as few as four neurons in series, although interneurons may also be interposed within the NTS.
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What are the roles of substance p and neurokinin-1 receptors in the control of negative chronotropic or negative Dromotropic vagal motoneurons? a physiological and ultrastructural analysis
Brain Research, 1996Co-Authors: V. J. Massari, Tannis A. Johnson, Richard A. Gillis, Philip J. GattiAbstract:Abstract Recent data indicate that there is a cardiotopic organization of negative chronotropic and negative Dromotropic neurons in the nucleus ambiguus (NA). Negative Dromotropic neurons are found in the rostral ventrolateral NA (rNA-VL), negative chronotropic neurons are found in the caudal ventrolateral NA (cNA-VL), and both types of neurons are found in an intermediate level of the ventrolateral NA (iNA-VL). Substance P (SP) immunoreactive nerve terminals synapse upon negative chronotropic vagal motoneurons in the iNA-VL, and SP microinjections in the NA cause bradycardia. In the present report we have attempted to: (1) define the type of tachykinin receptor which mediates the negative chronotropic effect of SP microinjections into the iNA-VL; (2) define the physiological effect of microinjections of a selective SP agonist into the rNA-VL on atrioventricular (AV) conduction; and (3) find ultrastructural evidence for synaptic interactions of SP-immunoreactive nerve terminals with negative Dromotropic vagal motoneurons in the rNA-VL. Microinjections of the excitatory amino acid glutamate (Glu) into the iNA-VL to activate all local vagal preganglionic neurons caused both bradycardia and a decrease in the rate of AV conduction. Injections of the selective neurokinin-1 (NK-1) receptor agonist drug GR-73632 also caused bradycardia, however the rapid onset of agonist induced desensitization prevented an evaluation of potential effects on AV conduction in the iNA-VL. These data suggest that the SP-induced bradycardia which can be elicited from the NA is mediated, at least in part, by NK-1 receptors. Microinjections of Glu into the rNA-VL caused a decrease in AV conduction without an effect on cardiac rate. On the other hand, GR-73632 microinjections into rNA-VL did not affect AV conduction. Following injections of the β subunit of cholera toxin conjugated to horseradish peroxidase (CTB-HRP) into the left atrial fat pad ganglion which selectively mediates changes in AV conduction, retrogradely labeled neurons were histochemically visualized in the rNA-VL. These tissues were subsequently processed for the simultaneous immunocytochemical visualization of SP, and examined by electron microflapy. Histochemically labeled neurons were large, multipolar, with abundant cytoplasm containing large masses of rough endoplasmic reticulum, and exhibited distinctive dendritic and somatic spines. Unlabeled nerve terminals were noted to form either asymmetric or symmetric synapses with dendrites, dendritic spines, and perikarya of histochemically labeled neurons. SP-immunoreactive nerve terminals were also detected in the rNA-VL. SP terminals typically contained numerous small pleomorphic vesicles, multiple large dense core vesicles, and several mitochondria, and they synapsed upon unlabeled dendritic profiles. A total of 154 SP-immunoreactive nerve terminals were observed on photomicrographs of tissues which also contained histochemically labeled profiles. None made an identifiable synapse with a retrogradely labeled profile on the sections examined. In summary, both physiological and ultrastructural data indicate that SP terminals in the iNA-VL do modify the output of negative chronotropic vagal motoneurons. This effect is mediated by NK-1 receptors. On the other hand both physiological and ultrastructural data indicate that SP terminals in the rNA-VL do not modify the output of negative Dromotropic vagal motoneurons. Therefore different mechanisms (neurotransmitters or receptors) mediate the central vagal control of cardiac rate and AV conduction.
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Research report Cardiotopic organization of the nucleus ambiguus? An anatomical and physiological analysis of neurons regulating atrioventricular conduction
1995Co-Authors: V. John Massari, Tannis A. Johnson, Philip J. GattiAbstract:Previous data indicate that there are anatomically segregated and physiologically independent parasympathetic postganglionic vagal motoneurons on the surface of the heart which are capable of selective control of sinoatrial rate, atrioventricular conduction and atrial contractility. We have injected a retrograde tracer into the cardiac ganglion which selectively regulates atrioventricular conduction (the AV ganglion). Medullary tissues were processed for the histochemical detection of retrogradely labeled neurons by light and electron microscopic methods. Negative Dromotropic retrogradely labeled cells were found in a long column in the ventrolateral nucleus ambiguus (NA-VL), which enlarged somewhat at the level of the area postrema, but reached its largest size rostral to the area postrema in an area termed the rostral ventrolateral nucleus ambiguus (rNA-VL). Three times as many cells were observed in the left rNA-VL as compared to the right (P < 0.025). Retrogradely labeled cells were also consistantly observed in the dorsal motor nucleus of the vagus (DMV). The DMV contained one third as many cells as the NA-VL. The right DMV contained twice as many cells as the left (P < 0.05). These data are consistent with physiological evidence that suggests that the left vagus nerve is dominant in the regulation of AV conduction, but that the right vagus nerve is also influential. While recording the electrocardiogram in paced and non-paced hearts, L-glutamate (GLU) was microinjected into the rNA-VL. Microinjections of GLU caused a 76% decrease in the rate of atrioventricular (AV) conduction (P < 0.05) and occasional second degree heart block, without changing heart rate. The effects of GLU were abolished by ipsilateral cervical vagotomy. These physiological data therefore support the anatomical inference that CNS neurons that are retrogradely labeled from the AV ganglion selectively exhibit negative Dromotropic properties. Retrogradely labeled negative Dromotropic neurons displayed a round nucleus with ample cytoplasm, abundant rough endoplasmic reticulum and the presence of distinctive somatic and dendritic spines. These neurons received synapses from afferent terminals containing small pleomorphic vesicles and large dense core vesicles. These terminals made both asymmetric and symmetric contacts with negative Dromotropic dendrites and perikarya, respectively. In conclusion, the data presented indicate that there is a cardiotopic organization of ultrastructurally distinctive negative Dromotropic neurons in the NA-VL. This central organization of parasympathetic preganglionic vagal motoneurons mirrors the functional organization of cardioinhibitory postganglionic neurons of the peripheral vagus nerve. These data are further discussed in comparison to a recent report on the light microscopic distribution and ultrastructural characteristics of negative chronotropic neurons in the NA-VL 42. The data support the hypothesis that anatomically separated and functionally selective parasympathetic preganglionic vagal motoneurons in the NA may independently control AV conduction and cardiac rate.
Miho Kasama - One of the best experts on this subject based on the ideXlab platform.
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Selective inhibition by a class III antiarrhythmic agent, E-4031, of the negative chronotropic response to parasympathetic stimulation in anesthetized dogs.
The Journal of pharmacology and experimental therapeutics, 1996Co-Authors: Hiroshi Imamura, Miho Kasama, Yuji Hoyano, Yasuyuki Furukawa, Hirofumi Nakano, Shigetoshi ChibaAbstract:To investigate the influence of a class III antiarrhythmic agent, E-4031, on the vagus control of the heart, we studied the effects of E-4031 on the chronotropic, Dromotropic and inotropic responses to parasympathetic stimulation in the autonomically decentralized hearts of the open-chest, anesthetized dogs. E-4031 (0.01-3 mumol/kg i.v.) decreased heart rate dose-dependently without affecting atrioventricular (AV) conduction time, first derivative of "a" wave component of the right atrial pressure (RA dP/dt), maximum rate of the right ventricular pressure development (RV +dP/dt) and arterial blood pressure. When cervical vagus stimulation decreased the heart rate, RA dP/dt and RV +dP/dt and prolonged the AV conduction time, E-4031 antagonized the negative chronotropic response in a dose-dependent manner but affected neither Dromotropic nor atrial inotropic responses. E-4031 at a high dose of 3 mumol/kg i.v. attenuated the ventricular inotropic response. ID50 for the chronotropism was 0.20 +/- 0.05 mumol/kg. Stimulation of the selective intracardiac parasympathetic nerves to the sinoatrial nodal area decreased the heart rate and RA dP/dt without a Dromotropic response. E-4031 antagonized the negative chronotropic response to the stimulation but not the inotropic response. Stimulation of the selective intracardiac parasympathetic nerves to the AV nodal area prolonged the AV conduction time without a chronotropic response. E-4031 at a high dose of 3 mumol/kg i.v. attenuated the negative Dromotropic response to the stimulation by 35 +/- 10%. These results suggest that E-4031 preferentially blocks the negative chronotropic response to vagus stimulation without significantly affecting other cardiac responses at a site distal to the muscarinic receptor in the heart in situ.
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Atrioventricular junctional rhythm induced by sympathetic stimulation in E-4031-treated dog hearts.
Journal of Cardiovascular Pharmacology, 1996Co-Authors: Hiroshi Imamura, Miho Kasama, Yuji Hoyano, Yasuyuki Furukawa, Hirofumi Nakano, Kyohei Yamazaki, Shigetoshi ChibaAbstract:To investigate the role of delayed rectifier potassium current (I K ) on the sympathetic control of the heart, we studied the effects of E-403 1, a blocker of the rapidly activating type of I K (I Kr ), on the chronotropic, Dromotropic, and inotropic responses to sympathetic nerve stimulation in the autonomically decentralized hearts of open-chest anesthetized dogs. E-4031 (0.01-3 μmol/kg intravenously, i.v.) decreased the heart rate (HR) dose dependently without affecting other cardiac functions. After E-4031 treatment, cardiac sympathetic nerve stimulation changed the sinus rhythm to the atrioventricular (AV) junctional rhythm in 6 of 11 anesthetized dogs (55%). In three of six junctional rhythm hearts, sinus rhythm supervened during sympathetic stimulation for 2 min. The number of pacemaker shifts to junctional rhythm increased as the dose of E-4031 was increased. However, E-4031 attenuated neither the positive chronotropic, Dromotropic, nor right atrial and ventricular inotropic responses to sympathetic nerve stimulation. These results suggest that I Kr inhibition may induce the AV junctional rhythm due to the combination of the different participation of I Kr , the different resting potentials, and the different sensitivity to sympathetic activation among cardiac pacemaker cells.
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selective inhibition by zatebradine and discrete parasympathetic stimulation of the positive chronotropic response to sympathetic stimulation in anesthetized dogs
Journal of Pharmacology and Experimental Therapeutics, 1995Co-Authors: Yasuyuki Furukawa, Miho Kasama, Yuji Hoyano, Takeshi Oguchi, Hirofumi Nakano, Shigetoshi ChibaAbstract:To investigate how to reduce the positive chronotropic response to sympathetic nerve activation selectively without affecting other cardiac actions, we studied the effects of zatebradine, an inhibitor of the hyperpolarization-activated current (I(f)), verapamil and parasympathetic nerve stimulation on the positive chronotropic, Dromotropic and inotropic responses to sympathetic nerve stimulation in the autonomically decentralized heart of the open-chest anesthetized dog. Parasympathetic input was activated by stimulation of the cervical vagus (CV) or parasympathetic nerves to the sinoatrial (SA) nodal region (SAP). Zatebradine (0.1-3 mumol/kg i.v.) decreased the heart rate but not other cardiac responses to sympathetic nerve stimulation, i.e., a wave component of the right atrial pressure (RAP), the first derivative of the RAP (dRAP/dt), atrioventricular (AV) conduction time (AVCT), right ventricular pressure (RVP) and its first derivative (dRVP/dt). Zatebradine (1 mumol/kg) inhibited basal heart rate by 28% but inhibited the chronotropic response to sympathetic stimulation by 85%. Verapamil (0.06-0.6 mumol/kg i.v.) attenuated the increases in heart rate, RVP and dRVP/dt elicited by sympathetic stimulation but potentiated shortening of the AVCT from the prolonged basal AVCT. The SAP stimulation attenuated the heart rate and dRAP/dt responses to sympathetic stimulation without affecting other cardiac responses, whereas CV stimulation decreased the positive chronotropic and atrial and ventricular inotropic responses. Cervical vagus stimulation did not change the positive Dromotropic response. These results demonstrate that in contrast to CV nerve activation or verapamil, zatebradine and SAP stimulation cause bradycardia but preserve the myocardial contractile force and AVCT in response to sympathetic nerve activation or sympathomimetic drugs in the heart in situ.
