Buñag R D, Davidow L W
Department of Pharmacology, Toxicology and Therapeutics, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City.
Aging (Milano). 1998 Apr;10(2):102-11. doi: 10.1007/BF03339644.
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.
为了确定酮色林长期治疗对心血管系统的影响是否会随年龄增长而变化，对4、14或24月龄的雄性斯普拉格-道利大鼠每日灌胃给予酮色林，持续14天。治疗前，24月龄大鼠的血压高于年轻大鼠，其反射性心率反应也较弱。酮色林治疗导致低血压、心动过缓增强、反射性心动过速减弱以及5-羟色胺（5-HT）反应逆转，所有这些效应在24月龄大鼠中比年轻大鼠更为明显。与年龄相关的效应均不能归因于α-肾上腺素能阻滞，因为即使在任何年龄对α1-肾上腺素能激动剂去氧肾上腺素的心血管反应未改变的情况下，这些效应仍然出现。另一方面，5-羟色胺能阻滞似乎是一个更合理的解释，因为酮色林对5-羟色胺心血管反应的逆转或增强与年龄相关，在14和24月龄大鼠中比在4月龄大鼠中更为显著。我们的结果表明，随着年龄增长，酮色林对心血管系统的作用愈发明显，5-HT阻滞增强，心动过缓加剧，直至随后的心脏抑制最终加重老年大鼠的低血压效应。
