HYPOTENSIVE AND REFLEX BRADYCARDIAC EFFECTS OF KETANSERIN, BUT NOT OFPRAZOSIN, ENHANCED SELECTIVELY IN AGING CONSCIOUS RATS

To determine whether cardiovascular effects of ketanserin are altered differently with aging as compared with those of prazosin, we recorded blood pressure (BP) and heart, rate (HR) changes produced by treatmen t with either drug in three age groups of conscious Sprague-Dawley rat s, BP was decreased more by ketanserin in 24-month than in 4- or 14-mo nth-old rats, but was decreased equally by prazosin in all age groups. Pressor responses to phenylephrine (PE) were consistently abolished b y both drugs, indicating that the greater hypotensive effects of ketan serin in 24-month-old rats were not due simply to alpha(1)-adrenergic blockade. By contrast, baroreflex sensitivity, determined from reflex HR responses to infused angiotensin or sodium nitroprusside (SNP), was altered differently in old rats by ketanserin but riot by prazosin. W hereas enhancement of reflex bradycardia by prazosin occurred at all a ges, it was demonstrable only with ketanserin in older rats. Moreover, reflex tachycardia was unaffected by prazosin but was reversed to bra dycardia by ketanserin in older rats. Because these differences persis ted even after the data had been normalized to compensate for differen ces in baseline pressures, effects on HR reflexes were considered age dependent for ketanserin but not for prazosin. Although the underlying mechanisms are not clear, the selective enhancement of reflex bradyca rdia and reversal of reflex tachycardia in old rats by ketanserin, but not by prazosin, could explain why hypotensive responses to ketanseri n increase with age whereas those to prazosin do not.