Cardiovascular effects of ketanserin in conscious rabbits

The antihypertensive effects of intravenous injection of ketanserin, a 5-HT2 receptor antagonist, were assessed in conscious rabbits. In intact rabbits, ketanserin lowered blood pressure in a dose-dependent manner. The antihypertensive effects of ketanserin were also observed in rabbits with two-kidney, one clip (2K1C) hypertension and with one-kidney, one clip (1K1C) hypertension. The effect was more marked in the 1K1C rabbits with low plasma renin activity (PRA) and high plasma norepinephrine (PNE) than in 2K1C rabbits with high PRA and normal PNE. The heart rate was not changed. Ketanserin suppressed the pressor response to exogenous norepinephrine (0.6 micrograms/Kg) 15, 30 and 45 min after the injection of ketanserin (1 mg/Kg). It also suppressed the pressor response to phenylephrine (3 micrograms/Kg) 15 min after the injection, but it did not suppress the pressor response to angiotensin II (0.15 micrograms/Kg). In order to investigate baroreceptor function, balloons were placed around the abdominal aorta and the inferior vena cava and inflated alternately. Thus, the mean arterial pressure vs heart period-logistic curve was obtained under steady-state conditions. There were no changes after the drug administration in the range of heart period and the gain (the slope at midpoint of the curve). These results suggest that the inhibition of pressor response of norepinephrine has effects in addition to a direct vasodilatory action and that an alteration of baroreceptor function is not involved in the antihypertensive effects of ketanserin.