Aging enhances serotonergic cardiovascular blockade by ketanserin in conscious rats.
We recorded cardiovascular responses to serotonin (5-HT) and to two selective serotonergic agonists following ketanserin treatment in 3 groups of conscious rats aged 4, 14 or 24 months. The selective agonists were DOI (5-HT2 agonist), and phenylbiguanide (5-HT3 agonist). Before ketanserin treatment, pressor responses to 5-HT or DOI were larger while reflex bradycardic responses to 5-HT or phenylbiguanide were smaller in 14- and 24-month than in 4-month-old rats. Ketanserin treatment lowered blood pressure consistently, and the ensuing hypotension was more pronounced in 14- and 24-month than in 4-month-old rats. Pressor responses to DOI were attenuated similarly in all rats, but those to 5-HT were reversed to depressor responses whose magnitude was smaller in 14- and 24-month than in 4-month-old rats. On the other hand, bradycardic 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 ketanserin was given, old rats had enhanced pressor responses to 5-HT2 agonists together with weakened bradycardic responses to 5-HT3 agonists. Following ketanserin treatment, 5-HT2 pressor 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 pronounced hypotension produced in old rats by ketanserin is due to two complementary effects on serotonergic receptors: blockade of 5-HT2 pressor responses coupled with selective enhancement of 5-HT3 bradycardic responses.
Davidow
L W
LW
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160.
Schmitz
T M
TM
Buñag
R D
RD
D000375:Aging; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D001645:Biguanides; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C008846:phenyl biguanide