Key result
Inhibition of nitric oxide synthase with L-NAME significantly enhanced the myocardial contractile response (dP/dtmax) to dobutamine (up to 317% vs 195%, P<0.001) and isoproterenol in dogs.
Why the study?
Does NOS inhibition augment myocardial contractile responses to beta-adrenergic stimulation in autonomically blocked dogs?
Does NOS inhibition augment myocardial contractile responses to beta-adrenergic stimulation in autonomically blocked dogs?
p-value: p=<0.001
Inhibition of nitric oxide synthase with L-NAME significantly enhances myocardial contractility in response to beta-adrenergic stimulation in vivo.
NOS inhibition may augment beta-adrenergic contractility in dogs; leaves open human relevance and requires clinical validation.
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.
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Keaney et al. (1996) studied Myocardial contractility. L-NAME (NOS inhibitor) with dobutamine or isoproterenol vs. Dobutamine or isoproterenol alone (before L-NAME) was evaluated on Peak first derivative of pressure (dP/dtmax) (p=<0.001). Inhibition of nitric oxide synthase with L-NAME significantly enhanced the myocardial contractile response (dP/dtmax) to dobutamine (up to 317% vs 195%, P<0.001) and isoproterenol in dogs.
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