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

Joshua M. Hare, John F. Keaney, Jean Luc Balligand, Joseph Loscalzo, Thomas W. Smith, Wilson S. Colucci

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149 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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