AGING ENHANCES SEROTONERGIC CARDIOVASCULAR BLOCKADE BY KETANSERIN IN CONSCIOUS RATS

We recorded cardiovascular responses to serotonin (5-HT) and to two se lective serotonergic agonists following ketanserin treatment in 3 grou ps of conscious rats aged 4, 14 or 24 months. The selective agonists w ere DOI (5-HT2 agonist), and phenylbiguanide (5-HT3 agonist). Before k etanserin treatment, presser responses to 5-HT or DOI were larger whil e reflex bradycardic responses to 5-HT or phenylbiguanide were smaller in 14- and 24-month than in 4-month-old rats. Ketanserin treatment lo wered blood pressure consistently, and the ensuing hypotension was mor e pronounced in 14- and 24-month than in 4-month-old rats. Pressor res ponses to DOI were attenuated similarly in all rats, but those to 5-HT were reversed to depressor responses whose magnitude was smaller in 1 4- and 24-month than in 4-month-old rats. On the other hand, bradycard ic responses to 5-HT and phenylbiguanide were enhanced in 14- and 24- but not in 4-month-old rats. Our results indicate that even before ket anserin was given, old rats had enhanced presser responses to 5-HT2 ag onists together with weakened bradycardic responses to 5-HT3 agonists. Following ketanserin treatment, 5-HT2 presser responses were blocked while 5-HT3 bradycardic responses were enhanced but only in old rats. These results are compatible with the interpretation that the more pro nounced hypotension produced in old rats by ketanserin is due to two c omplementary effects on serotonergic. receptors: blockade of 5-HT2 pre sser responses coupled with selective enhancement of 5-HT3 bradycardic responses.