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Norepinephrine-induced changes in rat heart function, metabolism, and weight are antagonized by carvedilol
T Nagano1, S O'Harrow, G Sponer
1Department of Physiology, University of Munich, Germany.
Insights
Carvedilol exhibits beta-receptor blocking effects in rats, similar to propranolol but less pronounced. It also demonstrated moderate vasodilating properties and dose-dependently antagonized norepinephrine
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Drug Metabolism
Background:
- Carvedilol is a beta-blocker with additional alpha-blocking activity.
- Understanding its effects on cardiac function and related pathways is crucial.
Purpose of the Study:
- To characterize the pharmacologic effects of carvedilol in intact rats.
- To compare carvedilol's beta-receptor blocking activity with propranolol.
- To investigate carvedilol's influence on norepinephrine-induced cardiac changes.
Main Methods:
- Intact rats received continuous intravenous infusions of carvedilol, prazosin, or propranolol.
- Responses to isoproterenol (beta-agonist) and phenylephrine (alpha-agonist) were measured.
- Effects of carvedilol on norepinephrine-induced cardiac function, heart weight, and cardiac glucose-6-phosphate dehydrogenase (G-6-PD) activity were assessed.
Main Results:
- Carvedilol demonstrated beta-receptor blocking actions, less potent than propranolol.
- Carvedilol exhibited moderate vasodilating effects, reducing diastolic aortic pressure and left ventricular systolic pressure.
- Carvedilol dose-dependently antagonized norepinephrine's effects on heart function and weight.
- Carvedilol attenuated norepinephrine-induced increases in cardiac G-6-PD activity.
Conclusions:
- Carvedilol possesses significant beta-receptor blocking and vasodilating properties in rats.
- Its effects on cardiac function and metabolism are dose-dependent and antagonize norepinephrine.
- These findings contribute to understanding carvedilol's cardiovascular pharmacology.
Abstract:
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.