Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation.
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 micrograms/min) and isoproterenol (0.1 and 0.5 microgram/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 peak first derivative of pressure (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 guanosine 3',5'-cyclic monophosphate content. These results suggest a role for NO in the control of myocardial contractility in response to beta-adrenergic stimulation in vivo.
Keaney
J F
JF
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Hare
J M
JM
Balligand
J L
JL
Loscalzo
J
J
Smith
T W
TW
Colucci
W S
WS
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels; D006152:Cyclic GMP / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D007267:Injections; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D016276:Ventricular Function
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D004280:Dobutamine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester