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

Joshua Hare, J. F. Keaney, J. L. Balligand, J. Loscalzo, T. W. Smith, W. S. Colucci

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

In vitro studies indicate that muscarinic cholinergic inhibition of β- adrenergic cardiac responses may be modulated in part by nitric oxide (NO). To evaluate the role of NO in parasympathetic inhibition of the β-adrenergic contractile response in vivo, we assessed the inotropic response to dobutamine before and during bilateral vagus nerve stimulation in closed- chest dogs. Dobutamine administration and vagal stimulation were repeated during intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl- L-arginine (L-NMMA, 10 μmol/min) and again following infusion of L-arginine (100 mg/kg). In eight dogs, intracoronary dobutamine infusion at rates of 25 and 50 μg/min increased peak +dP/dt by 131±24 and 168±22%, respectively (P < 0.0001). Vagal stimulation (2.5 Hz) attenuated the responses to dobutamine (25 and 50 μg/min) by 23±4 and 21±4%, respectively (P < 0.001). L-NMMA reduced (by 44-62%; P < 0.001) and L-arginine restored vagal inhibition of the dobutamine-stimulated inotropic response. In a second group of nine dogs, dobutamine was administered systemically to assure a constant concentration in the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the dobutamine-stimulated inotropic response (2.5 and 5.0 μg/kg per min) by 40±12% and 57±8%, respectively (P < 0.004). As with intracoronary dobutamine, L-NMMA diminished and L-arginine restored vagal inhibition of the inotropic response to dobutamine. Intracoronary infusion of atropine (12 μg/min) abolished the vagal inhibitory effect, and intracoronary infusion of 8-bromo-cyclic GMP (1 and 10 mM) caused a dose-dependent attenuation of the dobutamine-stimulated increase in +dP/dt. These data suggest that NO mediates, at least in part, vagal inhibition of the inotropic response to β- adrenergic stimulation by dobutamine, and thus may play a role in normal physiologic regulation of myocardial autonomic responses.

Original languageEnglish
Pages (from-to)360-366
Number of pages7
JournalJournal of Clinical Investigation
Volume95
Issue number1
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Dobutamine
Adrenergic Agents
Nitric Oxide
Dogs
omega-N-Methylarginine
Arginine
Cholinergic Agents
Vagus Nerve Stimulation
Coronary Circulation
Atropine
Nitric Oxide Synthase
Thorax

Keywords

  • β-adrenergic agonist
  • automatic nervous system
  • dP/dt
  • nitric oxide
  • vagus nerve

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hare, J., Keaney, J. F., Balligand, J. L., Loscalzo, J., Smith, T. W., & Colucci, W. S. (1995). Role of nitric oxide in parasympathetic modulation of β-adrenergic myocardial contractility in normal dogs. Journal of Clinical Investigation, 95(1), 360-366.

Role of nitric oxide in parasympathetic modulation of β-adrenergic myocardial contractility in normal dogs. / Hare, Joshua; Keaney, J. F.; Balligand, J. L.; Loscalzo, J.; Smith, T. W.; Colucci, W. S.

In: Journal of Clinical Investigation, Vol. 95, No. 1, 01.01.1995, p. 360-366.

Research output: Contribution to journalArticle

Hare, J, Keaney, JF, Balligand, JL, Loscalzo, J, Smith, TW & Colucci, WS 1995, 'Role of nitric oxide in parasympathetic modulation of β-adrenergic myocardial contractility in normal dogs', Journal of Clinical Investigation, vol. 95, no. 1, pp. 360-366.
Hare, Joshua ; Keaney, J. F. ; Balligand, J. L. ; Loscalzo, J. ; Smith, T. W. ; Colucci, W. S. / Role of nitric oxide in parasympathetic modulation of β-adrenergic myocardial contractility in normal dogs. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 1. pp. 360-366.
@article{98f3eac3dfa648f49b0006a83671d4dc,
title = "Role of nitric oxide in parasympathetic modulation of β-adrenergic myocardial contractility in normal dogs",
abstract = "In vitro studies indicate that muscarinic cholinergic inhibition of β- adrenergic cardiac responses may be modulated in part by nitric oxide (NO). To evaluate the role of NO in parasympathetic inhibition of the β-adrenergic contractile response in vivo, we assessed the inotropic response to dobutamine before and during bilateral vagus nerve stimulation in closed- chest dogs. Dobutamine administration and vagal stimulation were repeated during intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl- L-arginine (L-NMMA, 10 μmol/min) and again following infusion of L-arginine (100 mg/kg). In eight dogs, intracoronary dobutamine infusion at rates of 25 and 50 μg/min increased peak +dP/dt by 131±24 and 168±22{\%}, respectively (P < 0.0001). Vagal stimulation (2.5 Hz) attenuated the responses to dobutamine (25 and 50 μg/min) by 23±4 and 21±4{\%}, respectively (P < 0.001). L-NMMA reduced (by 44-62{\%}; P < 0.001) and L-arginine restored vagal inhibition of the dobutamine-stimulated inotropic response. In a second group of nine dogs, dobutamine was administered systemically to assure a constant concentration in the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the dobutamine-stimulated inotropic response (2.5 and 5.0 μg/kg per min) by 40±12{\%} and 57±8{\%}, respectively (P < 0.004). As with intracoronary dobutamine, L-NMMA diminished and L-arginine restored vagal inhibition of the inotropic response to dobutamine. Intracoronary infusion of atropine (12 μg/min) abolished the vagal inhibitory effect, and intracoronary infusion of 8-bromo-cyclic GMP (1 and 10 mM) caused a dose-dependent attenuation of the dobutamine-stimulated increase in +dP/dt. These data suggest that NO mediates, at least in part, vagal inhibition of the inotropic response to β- adrenergic stimulation by dobutamine, and thus may play a role in normal physiologic regulation of myocardial autonomic responses.",
keywords = "β-adrenergic agonist, automatic nervous system, dP/dt, nitric oxide, vagus nerve",
author = "Joshua Hare and Keaney, {J. F.} and Balligand, {J. L.} and J. Loscalzo and Smith, {T. W.} and Colucci, {W. S.}",
year = "1995",
month = "1",
day = "1",
language = "English",
volume = "95",
pages = "360--366",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

TY - JOUR

T1 - Role of nitric oxide in parasympathetic modulation of β-adrenergic myocardial contractility in normal dogs

AU - Hare, Joshua

AU - Keaney, J. F.

AU - Balligand, J. L.

AU - Loscalzo, J.

AU - Smith, T. W.

AU - Colucci, W. S.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - In vitro studies indicate that muscarinic cholinergic inhibition of β- adrenergic cardiac responses may be modulated in part by nitric oxide (NO). To evaluate the role of NO in parasympathetic inhibition of the β-adrenergic contractile response in vivo, we assessed the inotropic response to dobutamine before and during bilateral vagus nerve stimulation in closed- chest dogs. Dobutamine administration and vagal stimulation were repeated during intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl- L-arginine (L-NMMA, 10 μmol/min) and again following infusion of L-arginine (100 mg/kg). In eight dogs, intracoronary dobutamine infusion at rates of 25 and 50 μg/min increased peak +dP/dt by 131±24 and 168±22%, respectively (P < 0.0001). Vagal stimulation (2.5 Hz) attenuated the responses to dobutamine (25 and 50 μg/min) by 23±4 and 21±4%, respectively (P < 0.001). L-NMMA reduced (by 44-62%; P < 0.001) and L-arginine restored vagal inhibition of the dobutamine-stimulated inotropic response. In a second group of nine dogs, dobutamine was administered systemically to assure a constant concentration in the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the dobutamine-stimulated inotropic response (2.5 and 5.0 μg/kg per min) by 40±12% and 57±8%, respectively (P < 0.004). As with intracoronary dobutamine, L-NMMA diminished and L-arginine restored vagal inhibition of the inotropic response to dobutamine. Intracoronary infusion of atropine (12 μg/min) abolished the vagal inhibitory effect, and intracoronary infusion of 8-bromo-cyclic GMP (1 and 10 mM) caused a dose-dependent attenuation of the dobutamine-stimulated increase in +dP/dt. These data suggest that NO mediates, at least in part, vagal inhibition of the inotropic response to β- adrenergic stimulation by dobutamine, and thus may play a role in normal physiologic regulation of myocardial autonomic responses.

AB - In vitro studies indicate that muscarinic cholinergic inhibition of β- adrenergic cardiac responses may be modulated in part by nitric oxide (NO). To evaluate the role of NO in parasympathetic inhibition of the β-adrenergic contractile response in vivo, we assessed the inotropic response to dobutamine before and during bilateral vagus nerve stimulation in closed- chest dogs. Dobutamine administration and vagal stimulation were repeated during intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl- L-arginine (L-NMMA, 10 μmol/min) and again following infusion of L-arginine (100 mg/kg). In eight dogs, intracoronary dobutamine infusion at rates of 25 and 50 μg/min increased peak +dP/dt by 131±24 and 168±22%, respectively (P < 0.0001). Vagal stimulation (2.5 Hz) attenuated the responses to dobutamine (25 and 50 μg/min) by 23±4 and 21±4%, respectively (P < 0.001). L-NMMA reduced (by 44-62%; P < 0.001) and L-arginine restored vagal inhibition of the dobutamine-stimulated inotropic response. In a second group of nine dogs, dobutamine was administered systemically to assure a constant concentration in the coronary circulation. Vagal stimulation (2.5 Hz) attenuated the dobutamine-stimulated inotropic response (2.5 and 5.0 μg/kg per min) by 40±12% and 57±8%, respectively (P < 0.004). As with intracoronary dobutamine, L-NMMA diminished and L-arginine restored vagal inhibition of the inotropic response to dobutamine. Intracoronary infusion of atropine (12 μg/min) abolished the vagal inhibitory effect, and intracoronary infusion of 8-bromo-cyclic GMP (1 and 10 mM) caused a dose-dependent attenuation of the dobutamine-stimulated increase in +dP/dt. These data suggest that NO mediates, at least in part, vagal inhibition of the inotropic response to β- adrenergic stimulation by dobutamine, and thus may play a role in normal physiologic regulation of myocardial autonomic responses.

KW - β-adrenergic agonist

KW - automatic nervous system

KW - dP/dt

KW - nitric oxide

KW - vagus nerve

UR - http://www.scopus.com/inward/record.url?scp=0028821656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028821656&partnerID=8YFLogxK

M3 - Article

VL - 95

SP - 360

EP - 366

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -