Inhibition of nitric oxide synthase augments myocardial contractile
responses to [beta]-adrenergic stimulation.
Keaney, John F., Joshua M. Hare, Jean-Luc Balligand, Joseph Loscalzo,
Thomas W. Smith, and Wilson S. Colucci.
Cardiovascular Division, Department of Medicine, Brigham and
Women's Hospital, Boston, MA, 02115, Brockton/West Roxbury VA Medical
Center, West Roxbury, MA, 02132; Harvard Medical School, Boston, MA,
02115
APStracts 3:0241H, 1996.
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 [beta]-adrenergic stimulation in
autonomically-blocked dogs. Intracoronary infusions of dobutamine (1
- 50 [mu]g/min) and isoproterenol (0.1 and 0.5 [mu]g/min) were
performed before and after the intracoronary administration of the
specific NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME).
Intracoronary dobutamine resulted in a dose-dependent increase in
dP/dtmax 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/dtmax increasing 276% +/- 17% and 317% +/- 26%, respectively
(P<0.001). Intracoronary isoproterenol resulted in a maximum
increase in dP/dtmax 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/dtmax but did produce a reduction in
myocardial cGMP content. These results suggest a role for NO in the
control of myocardial contractility in response to [beta]-adrenergic
stimulation in vivo.
Received 14 February 1996; accepted in final form 29 May 1996.
APS Manuscript Number H150-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96