Hypotensive and reflex bradycardic effects of ketanserin, but not of prazosin, 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 treatment with either drug in three age groups of conscious Sprague-Dawley rats. BP was decreased more by ketanserin in 24-month than in 4- or 14-month-old rats, but was decreased equally by prazosin in all age groups. Pressor responses to phenylephrine (PE) were consistently abolished by both drugs, indicating that the greater hypotensive effects of ketanserin 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 not by prazosin. Whereas enhancement of reflex bradycardia by prazosin occurred at all ages, it was demonstrable only with ketanserin in older rats. Moreover, reflex tachycardia was unaffected by prazosin but was reversed to bradycardia by ketanserin in older rats. Because these differences persisted even after the data had been normalized to compensate for differences 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 bradycardia and reversal of reflex tachycardia in old rats by ketanserin, but not by prazosin, could explain why hypotensive responses to ketanserin increase with age whereas those to prazosin do not.
Davidow
L W
LW
Department of Pharmacology, Toxicology and Therapeutics, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City 66160-7417, USA.
Buñag
R D
RD
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009599:Nitroprusside; D010656:Phenylephrine; D007650:Ketanserin; D011224:Prazosin