Inhibition of nitric oxide synthase augments myocardial contractile responses to β-adrenergic stimulation

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

Research output: Contribution to journalArticle

Abstract

Recent in vitro evidence suggests a role for nitric oxide (NO) in the modulation of myocardial contractility. The specific role of NO in the control of cardiac function in vivo, however, remains unclear. We investigated the effect of NO synthase (NOS) inhibition on myocardial contractility in response to β-adrenergic stimulation in autonomically blocked dogs. Intracoronary infusions of dobutamine (1-50 μg/min) and isoproterenol (0.1 and 0.5 μg/min) were performed before and after the intracoronary administration of the specific NOS inhibitor N(G)-nitro-L- arginine methyl ester (L-NAME). Intracoronary dobutamine resulted in a dose- dependent increase in peak first derivative of pressure (dP/dt(max)) to a maximum of 195 ± 10% (P <0.001). After inhibition of NOS with intracoronary L-NAME at rates of 0.1 and 1 mg/min, the response to dobutamine was significantly enhanced with dP/dt(max), increasing 276 ± 17 and 317 ± 26%, respectively (P <0.001). Intracoronary isoproterenol resulted in a maximum increase in dP/dt(max) of 116 ± 15% (P <0.001) that further increased to 154 ± 17 and 157 ± 18% after NOS inhibition with 0.1 and 1 mg/min L-NAME, respectively (both P <0.002). L-NAME had no effect on baseline dP/dt(max) but did produce a reduction in myocardial guanosine 3',5'-cyclic monophosphate content. These results suggest a role for NO in the control of myocardial contractility in response to β-adrenergic stimulation in vivo.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume271
Issue number6 40-6
StatePublished - 1996
Externally publishedYes

Fingerprint

NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Adrenergic Agents
Dobutamine
Nitric Oxide
Isoproterenol
Cyclic GMP
Dogs
Pressure

Keywords

  • dobutamine
  • guanosine 3',5'-cyclic monophosphate
  • isoproterenol
  • N(G)-nitro-L-arginine methyl ester

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Keaney, J. F., Hare, J. M., Balligand, J. L., Loscalzo, J., Smith, T. W., & Colucci, W. S. (1996). Inhibition of nitric oxide synthase augments myocardial contractile responses to β-adrenergic stimulation. American Journal of Physiology - Heart and Circulatory Physiology, 271(6 40-6).

Inhibition of nitric oxide synthase augments myocardial contractile responses to β-adrenergic stimulation. / Keaney, John F.; Hare, Joshua M.; Balligand, Jean Luc; Loscalzo, Joseph; Smith, Thomas W.; Colucci, Wilson S.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 271, No. 6 40-6, 1996.

Research output: Contribution to journalArticle

Keaney, John F. ; Hare, Joshua M. ; Balligand, Jean Luc ; Loscalzo, Joseph ; Smith, Thomas W. ; Colucci, Wilson S. / Inhibition of nitric oxide synthase augments myocardial contractile responses to β-adrenergic stimulation. In: American Journal of Physiology - Heart and Circulatory Physiology. 1996 ; Vol. 271, No. 6 40-6.
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