Does chronic ketanserin treatment enhance bradycardia in old rats by serotonergic blockade?
To determine if the cardiovascular effects of chronic treatment with ketanserin would vary with increasing age, ketanserin was given by daily gavage for 14 days to male Sprague-Dawley rats at ages 4, 14, or 24 months. Before treatment, 24-month-old rats had higher blood pressures and weaker reflex heart rate responses than younger rats. Treatment with ketanserin caused hypotension, enhanced bradycardia, attenuated reflex tachycardia, and reversed serotonin (5-HT) responses, with all effects being more pronounced in 24-month-old rats than in younger rats. None of the age-related effects can be attributed to alpha-adrenergic blockade because they occurred even while cardiovascular responses to phenylephrine, an alpha 1-adrenergic agonist, were unaltered at any age. On the other hand, serotonergic blockade seems a more likely explanation because reversal or enhancement by ketanserin of cardiovascular responses to serotonin was age-related, being more marked in 14- and 24- than in 4-month-old rats. Our results suggest that as the cardiovascular effects of ketanserin become more pronounced with advancing age, 5-HT blockade intensifies and bradycardia becomes augmented until the ensuing cardiac inhibition eventually accentuates the hypotensive effects in older rats.
Department of Pharmacology, Toxicology and Therapeutics, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City.
R D
RD
Buñag
L W
LW
Davidow
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D001919:Bradycardia / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D007650:Ketanserin / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D013610:Tachycardia / Q000139:chemically induced
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D012702:Serotonin Antagonists; D010656:Phenylephrine; D012701:Serotonin; D007650:Ketanserin