Davidow L W, Schmitz T M, Buñag R D
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160.
Aging (Milano). 1994 Aug;6(4):239-48. doi: 10.1007/BF03324249.
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.
我们记录了3组4、14或24月龄清醒大鼠在给予酮色林治疗后对血清素（5-羟色胺，5-HT）以及两种选择性5-羟色胺能激动剂的心血管反应。这两种选择性激动剂分别是DOI（5-HT2激动剂）和苯乙双胍（5-HT3激动剂）。在给予酮色林治疗前，14月龄和24月龄大鼠对5-HT或DOI的升压反应较大，而对5-HT或苯乙双胍的反射性心动过缓反应较小，相比之下，4月龄大鼠的上述反应则相反。酮色林治疗可持续降低血压，且随后出现的低血压在14月龄和24月龄大鼠中比4月龄大鼠更为明显。所有大鼠对DOI的升压反应均有类似程度的减弱，但对5-HT的升压反应则转变为降压反应，且14月龄和24月龄大鼠降压反应的幅度小于4月龄大鼠。另一方面，14月龄和24月龄大鼠对5-HT和苯乙双胍的心动过缓反应增强，而4月龄大鼠则未增强。我们的结果表明，即使在给予酮色林之前，老年大鼠对5-HT2激动剂的升压反应增强，同时对5-HT3激动剂的心动过缓反应减弱。给予酮色林治疗后，5-HT2升压反应被阻断，而5-HT3心动过缓反应增强，但仅在老年大鼠中出现。这些结果符合以下解释：酮色林在老年大鼠中产生的更明显的低血压是由于对5-羟色胺能受体的两种互补作用所致，即阻断5-HT2升压反应并选择性增强5-HT3心动过缓反应。
