Analysis of the mechanism underlying the vasodilator action of carvedilol in pithed spontaneously hypertensive rats.

The present experiments were carried out to examine the vasodilator mechanism(s) of carvedilol by use of pithed spontaneously hypertensive rats (SHR). Animals were pithed and the dose-pressor response curves to various agonists were obtained 0.5 or 1 hour after oral administration of either carvedilol (30 mg/kg), labetalol (60 mg/kg), prazosin (0.1 mg/kg) or hydralazine (3 mg/kg). These doses of drugs caused approximately equihypotensive responses in the conscious state. Carvedilol significantly shifted the dose-pressor response curve to the right for phenylephrine but not for B-HT 920, angiotensin II and vasopressin. Labetalol and prazosin also significantly shifted the dose-response curve to the right for phenylephrine but not for angiotensin II. The rank order of inhibitory action on the phenylephrine response was prazosin greater than labetalol greater than carvedilol. In addition, carvedilol produced a slight but significant inhibition of the pressor responses to serotonin (5-hydroxytryptamine), which was nearly identical in magnitude to that seen with hydralazine. These results suggest that the vasodilator action of carvedilol is mainly attributed to alpha 1-adrenoceptor blockade, although additional non-adrenergic mechanism(s) of action cannot be excluded.