Carvedilol significantly decreased mean arterial pressure (from 126.6 to 75.9 mm Hg, P<.001) and increased NO levels, effects that were abolished by NOS inhibition with L-NAME.
Does carvedilol decrease blood pressure via endogenous nitric oxide production in male Wistar rats?
The hemodynamic and blood pressure-lowering effects of carvedilol are partially dependent on the endogenous production of nitric oxide.
p-value: p=<.001
BACKGROUND: Carvedilol is known to be an adrenoreceptor blocker and free radical scavenger, used in hypertension and cardiac failure. However, its therapeutic actions cannot be fully explained by these mechanisms. In these studies, we tested the hypothesis that carvedilol action is associated with the synthesis/release of nitric oxide (NO). METHODS: Male Wistar rats (n = 22), 9 weeks old, were anesthetized with an intraperitoneal injection of sodium pentobarbital. Mean arterial pressure and arterial NO levels were monitored throughout the experiments. Carvedilol (1 mg/kg, intravenously iv) effects were evaluated before and after NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg, iv). RESULTS: Carvedilol induced a significant decrease in basal arterial pressure (from 126.6 +/- 4.3 mm Hg to 75.9 +/- 3.0 mm Hg, P < .001) and significant increase in NO levels (from 17.9 +/- 1.7 micromol/L to 32.2 +/- 2.5 micromol/L, P < .001). After administration of L-NAME the arterial pressure increased (129.9 +/- 5.0 mm Hg, P < .001) with concomitant decrease in NO levels (13.4 +/- 1.6 micromol/L, P < .01). The second carvedilol administration (post-L-NAME) did not affect either arterial pressure (108.3 +/- 8.0 mm Hg) or NO levels (22.1 +/- 1.3 micromol/L). CONCLUSIONS: Our results suggest that the carvedilol-induced decrease of blood pressure is associated with an increase of plasma NO levels. Furthermore, NOS inhibition results in impairment of carvedilol hemodynamic effects and plasma NO levels. Therefore, these results are consistent with the hypothesis that the hemodynamic effect of carvedilol is in part dependent on endogenous NO production.
Afonso et al. (Fri,) reported a other. Carvedilol vs. Baseline and post-L-NAME (NOS inhibitor) was evaluated on Mean arterial pressure (p=<.001). Carvedilol significantly decreased mean arterial pressure (from 126.6 to 75.9 mm Hg, P<.001) and increased NO levels, effects that were abolished by NOS inhibition with L-NAME.