Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation

Broten, Theodore P.; Miyashiro, Jody K.; Moncada, S.; Feigl, Eric O.

doi:10.1152/ajpheart.1992.262.5.h1579

Cited by 76 publications

(71 citation statements)

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“…NO is involved in vagally mediated pulmonary (18) and coronary vasodilation (19), and in nonadrenergic, noncholinergic neurotransmission in animals (20,21) and humans (22,23 Experimental protocols Intracoronary dobutamine. Animals were allowed to stabilize for 30 min after instrumentation.…”

Section: -Adrenergic Agonistmentioning

confidence: 99%

“…The intraaortic balloon was inflated in a graded fashion with an inflation device (model SM 2500; SciMed, Maple Grove, MN) to maintain BP within 10 mmHg at a given dobutamine dose with and without vagal stimulation. Inhibition of NOS was achieved by intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA; CalbiochemNovabiochem Corp., La Jolla, CA) at a rate of 10 ,umol/min which yields a coronary concentration of 100 MM, assuming a total left coronary flow of 100 ml/min (19). After a 20-min infusion of L-NMMA and during concurrent administration of L-NMMA, vagal nerve stimulation was repeated without and with intracoronary infusion of dobutamine.…”

Section: -Adrenergic Agonistmentioning

confidence: 99%

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Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs.

Hare¹,

et al. 1995

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IntroductionIn vitro studies indicate that muscarinic cholinergic inhibition of 18-adrenergic cardiac responses may be modulated in part by nitric oxide (NO). The sympathetic and parasympathetic limbs of the autonomic nervous system play important and countervailing roles in regulating heart rate, atrioventricular conduction, and myocardial contractility. Sympathetic stimulation increases heart rate, conduction, and contractility, whereas parasympathetic stimulation slows both sinus node rate and atrioventricular conduction (1-6). Although it has little effect on ventricular contractility under basal conditions, an increase in vagal nerve activity attenuates the contractile response to sympathetic stimulation (1, 4) and infused 6-adrenergic agonists (2, 3, 5, 6). Likewise, the intracoronary infusion of acetylcholine attenuates the inotropic response to sympathetic nerve stimulation (5) and infused f3-adrenergic agonists (5, 6).There is evidence to suggest that nitric oxide (NO)' may influence the autonomic regulation of cardiac function. In isolated myocytes, NO has been shown to play a role in both muscarinic-cholinergic slowing of heart rate and attenuation of the contractile response to /3-adrenergic stimulation (7). NO acts by stimulating soluble guanylyl cyclase (8-10) to produce cyclic GMP (cGMP). In the heart, muscarinic-cholinergic stimulation also leads to increased cGMP production (11)(12)(13)(14)(15) which, in turn, may counteract the contractile effects of cAMP (16,17). Thus, there is theoretical support for the thesis that NO plays a role in modulating the interaction between the adrenergic and cholinergic arms of the autonomic nervous system.Despite the well-characterized role of NO in modulating myocyte function in vitro, the role of NO in modulating myocardial contractility in vivo remains undefined. NO is involved in vagally mediated pulmonary (18)

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Section: -Adrenergic Agonistmentioning

confidence: 99%

Section: -Adrenergic Agonistmentioning

confidence: 99%

Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs.

Hare¹,

et al. 1995

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“…It has nevertheless been suggested that acetylcholine released from parasympathetic adventitial nerves diffuses to the endothelium in concentrations sufficient to stimulate NO synthesis in the coronary and pulmonary circulations, on the basis that vasodilatation induced by vagal stimulation is blocked not only by atropine, but also by L-NAME (Broten, Miyashiro, Moncada & Feigl, 1992;McMahon, Hood & Kadowitz, 1992). This point requires further evaluation, however, as the effects of subsequent administration of L-arginine were not tested, and L-NAME and other alkylated esters of L-arginine may irreversibly bind to MI, M2 and M3 muscarinic receptors (Buxton, Cheek, Eckman, Westfall, Sanders & Keef, 1993).…”

Section: Flow-induced Release Of Endothelium-dependent Agonistsmentioning

confidence: 99%

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

Tm¹

1994

Experimental Physiology

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“…NO is recognized as a major endothelium-derived relaxing factor (1), and has been shown to participate in parasympathetic coronary vasodilation (2,3) and in inhibition of sympathetic peripheral and coronary vasoconstriction (4,5). NO has been shown to modulate myocardial contractility in response to both cholinergic (6, 7) and ␤ -adrenergic (8) stimulation.…”

Section: Introductionmentioning

confidence: 99%

Interaction between neuronal nitric oxide synthase and inhibitory G protein activity in heart rate regulation in conscious mice.

Jumrussirikul¹,

Dinerman²,

Dawson³

et al. 1998

J. Clin. Invest.

114

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Nitric oxide (NO) synthesized within mammalian sinoatrial cells has been shown to participate in cholinergic control of heart rate (HR). However, it is not known whether NO synthesized within neurons plays a role in HR regulation. HR dynamics were measured in 24 wild-type (WT) mice and 24 mice in which the gene for neuronal NO synthase (nNOS) was absent (nNOS Ϫ / Ϫ mice). Mean HR and HR variability were compared in subsets of these animals at baseline, after parasympathetic blockade with atropine (0.5 mg/kg i.p.), after ␤ -adrenergic blockade with propranolol (1 mg/kg i.p.), and after combined autonomic blockade. Other animals underwent pressor challenge with phenylephrine (3 mg/kg i.p.) after ␤ -adrenergic blockade to test for a baroreflex-mediated cardioinhibitory response. The latter experiments were then repeated after inactivation of inhibitory G proteins with pertussis toxin (PTX) (30 g/kg i.p.). At baseline, nNOS Ϫ / Ϫ mice had higher mean HR (711 Ϯ 8 vs. 650 Ϯ 8 bpm, P ϭ 0.0004) and lower HR variance (424 Ϯ 70 vs. 1,112 Ϯ 174 bpm 2 , P ϭ 0.001) compared with WT mice. In nNOS Ϫ / Ϫ mice, atropine administration led to a much smaller change in mean HR ( Ϫ 2 Ϯ 9 vs. 49 Ϯ 5 bpm, P ϭ 0.0008) and in HR variance (64 Ϯ 24 vs. Ϫ 903 Ϯ 295 bpm 2 , P ϭ 0.02) than in WT mice. In contrast, propranolol administration and combined autonomic blockade led to similar changes in mean HR between the two groups. After ␤ -adrenergic blockade, phenylephrine injection elicited a fall in mean HR and rise in HR variance in WT mice that was partially attenuated after treatment with PTX. The response to pressor challenge in nNOS Ϫ / Ϫ mice before PTX administration was similar to that in WT mice. However, PTX-treated nNOS Ϫ / Ϫ mice had a dramatically attenuated response to phenylephrine. These findings suggest that the absence of nNOS activity leads to reduced baseline parasympathetic tone, but does not prevent baroreflex-mediated cardioinhibition unless inhibitory G proteins are also inactivated. Thus, neuronally derived NO and cardiac inhibitory G protein activity serve as parallel pathways to mediate autonomic slowing of heart rate in the mouse. ( J. Clin. Invest.

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Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation

Cited by 76 publications

References 0 publications

Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs.

Role of nitric oxide in parasympathetic modulation of beta-adrenergic myocardial contractility in normal dogs.

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

Interaction between neuronal nitric oxide synthase and inhibitory G protein activity in heart rate regulation in conscious mice.

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