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Studies on the Antihypertensive Properties of Carvedilol, a Compound with &bgr;‐Blocking and Vasodilating Effects

Summary: The purpose of this study was to examine the antihypertensive effect of carvedilol and the possible mode of its action. After single oral administration, carvedilol (3–30 mg/kg) produced dose‐related decreases in systolic blood pressure (SBP) and heart rate in conscious hypertensive models: spontaneous hypertensive rats (SHR), renal hypertensive rats (one kidney, one clip), and deoxycorticosterone acetate (DOCA)/salt rats. Repeated administration of carvedilol (10 mg/kg, p.o., once daily for 5 days) caused a fall in SBP and bradycardia in SHR. The development of tolerance and the rebound phenomenon of SBP were not seen. In anesthetized SHR, the hypotensive response to carvedilol (0.3 mg/kg, i.v.), unlike that to propranolol, was accompanied by a significant reduction of total peripheral resistance. A tendency toward a decrease in plasma renin activity was observed after oral carvedilol in SHR. The hypotensive effect was not attenuated by the pretreatment of SHR with indomethacin. Further, carvedilol did not cause appreciable changes in the production of 6‐ketoprostaglandin (PG) F1&agr; in the aortic rings of SHR. In anesthetized cats, carvedilol (0.1 mg/kg, i.v.) produced a significant decrease in blood pressure but the same dose in the cerebral ventricle caused no detectable fall in blood pressure. The significant fall in blood pressure was observed in both intact and debuffered cats. These results suggest that carvedilol may possess a broad hypotensive spectrum against various types of experimental hypertension, and that the endogenous PG system and the central cardiovascular control system may not be responsible for the antihypertensive effect of carvedilol.