DOES CHRONIC KETANSERIN TREATMENT ENHANCE BRADYCARDIA IN OLD RATS BY SEROTONERGIC BLOCKADE

To determine if the cardiovascular effects of chronic treatment with k etanserin would vary with increasing age, ketanserin was given by dail y gavage for 14 days to merle Sprague-Dawley rats at ages 4, 14, or 24 months. Before treatment, 24-month-old rats had higher blood pressure s and weaker reflex heart rate responses than younger rats. Treatment with ketanserin caused hypotension, enhanced bradycardia, attenuated r eflex tachycardia, and reversed serotonin (5-HT) responses, with all e ffects being more pronounced in 24-month-old rats than in younger rats . None of the age-related effects can be attributed to alpha-adrenergi c blockade because they occurred even while cardiovascular responses t o phenylephrine, an alpha(1)-adrenergic agonist, were unaltered at any age. On the other hand, serotonergic blockade seems a more likely exp lanation because reversal or enhancement by ketanserin of cardiovascul ar responses to serotonin was age-related, being more marked in 14- an d 24- than in 4-month-old rats. Our results suggest that as the cardio vascular effects of ketanserin become more pronounced with advancing a ge, 5-HT blockade intensifies and bradycardia becomes augmented until the ensuing cardiac inhibition eventually accentuates the hypotensive effects in older rats. (Aging Clin. Exp. Res. 10: 102-111, 1998) (C)19 98, Editrice Kurtis.