Interference of ketanserin with baroreflex control of the circulation in the conscious spontaneously hypertensive rat

Abstract

Ketanserin suppresses baroreflex-mediated tachycardia following the administration of hypotensive doses of sodium nitroprusside in conscious spontaneously hypertensive rats (SHR). The purpose of this study was to compare the baroreflex effects of ketanserin with those of the more selective S2-serotonergic receptor antagonist ritanserin and the alpha 1-blocker prazosin. In conscious SHR, both ketanserin (3 mg/kg) and prazosin (0.01 and 0.1 mg/kg) caused a significant reduction in blood pressure. Ritanserin (3 mg/kg) and the combination of a low dose of prazosin (0.01 mg/kg) and ritanserin (3 mg/kg) did not lower blood pressure significantly. Baroreflex responses were determined by measuring the maximal changes in heart period (HP = 60,000/HR) after administration of 20 to 100 micrograms/kg sodium nitroprusside. Whereas saline and prazosin lacked an effect on changes in HPmax, ketanserin reversed the decrease in delta HPmax into a significant increase. Ritanserin alone caused a slight but insignificant inhibition, whereas the combination of ritanserin and prazosin blocked the sodium nitroprusside-induced reflex tachycardia. Ritanserin, in contrast to prazosin or ketanserin, lowered resting heart rate values. We conclude that the interference of ketanserin with the baroreflex in SHR is a unique property of this agent, related to its simultaneous effects on serotonin (5-HT) S2-receptors and alpha 1-adrenoceptors.