Norepinephrine-induced changes in rat heart function, metabolism, and weight are antagonized by carvedilol.

One aim of our study was to characterize in intact rats the pharmacologic effects of carvedilol. After 3 days of continuous intravenous (i.v.) infusion of carvedilol (0.5 mg/kg/h), the positive chronotropic and inotropic effects of i.v. bolus injections of isoproterenol (0.1, 0.3, and 1 microgram/kg) and phenylephrine (3, 10, and 30 micrograms/kg), respectively, were measured and compared with those obtained in rats that received a continuous i.v. infusion of 0.9% NaCl, prazosin (0.1 mg/kg/h), and propranolol (0.5 mg/kg/h). The chronotropic response to isoproterenol was less blunted in carvedilol-treated animals than in propranolol-treated animals. The pressure response to phenylephrine was attenuated only moderately. Thus, carvedilol had beta-receptor blocking actions on intact rat heart that were similar to but not as pronounced as those of propranolol. Because it reduced diastolic aortic pressure (DAP) and left ventricular systolic pressure (LVSP), it also had a moderate vasodilating effect. Carvedilol (continuous i.v. infusion of 0.25 and 0.5 mg/kg/h) antagonized the effects of norepinephrine (NE, i.v. infusion of 0.2 mg/kg/h for 3 days) on heart function and heart weight in a dose-dependent manner. It also attenuated markedly the norepinephrine (NE)-induced increase in the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (PPP), although a 37% stimulation persisted.