Davidow L W, Buñag R D
Department of Pharmacology, Toxicology and Therapeutics, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City 66160-7417, USA.
J Cardiovasc Pharmacol. 1996 Aug;28(2):294-301. doi: 10.1097/00005344-199608000-00017.
To determine whether cardiovascular effects of ketanserin are altered differently with aging as compared with those of prazosin, we recorded blood pressure (BP) and heart rate (HR) changes produced by treatment with either drug in three age groups of conscious Sprague-Dawley rats. BP was decreased more by ketanserin in 24-month than in 4- or 14-month-old rats, but was decreased equally by prazosin in all age groups. Pressor responses to phenylephrine (PE) were consistently abolished by both drugs, indicating that the greater hypotensive effects of ketanserin in 24-month-old rats were not due simply to alpha 1-adrenergic blockade. By contrast, baroreflex sensitivity, determined from reflex HR responses to infused angiotensin or sodium nitroprusside (SNP), was altered differently in old rats by ketanserin but not by prazosin. Whereas enhancement of reflex bradycardia by prazosin occurred at all ages, it was demonstrable only with ketanserin in older rats. Moreover, reflex tachycardia was unaffected by prazosin but was reversed to bradycardia by ketanserin in older rats. Because these differences persisted even after the data had been normalized to compensate for differences in baseline pressures, effects on HR reflexes were considered age dependent for ketanserin but not for prazosin. Although the underlying mechanisms are not clear, the selective enhancement of reflex bradycardia and reversal of reflex tachycardia in old rats by ketanserin, but not by prazosin, could explain why hypotensive responses to ketanserin increase with age whereas those to prazosin do not.
为了确定与哌唑嗪相比，酮色林的心血管效应是否会随衰老而产生不同变化，我们记录了清醒的斯普拉格 - 道利大鼠三个年龄组中使用这两种药物治疗所产生的血压（BP）和心率（HR）变化。与4个月或14个月大的大鼠相比，酮色林使24个月大的大鼠血压下降得更多，但哌唑嗪在所有年龄组中使血压下降的程度相同。两种药物均能持续消除对去氧肾上腺素（PE）的升压反应，这表明酮色林在24个月大的大鼠中更大的降压作用并非仅仅由于α1 - 肾上腺素能阻断。相比之下，通过对输注血管紧张素或硝普钠（SNP）的反射性HR反应测定的压力反射敏感性，在老年大鼠中，酮色林使其发生了不同的改变，而哌唑嗪则没有。虽然哌唑嗪在所有年龄段都能增强反射性心动过缓，但只有在老年大鼠中使用酮色林时才能表现出来。此外，反射性心动过速不受哌唑嗪影响，但在老年大鼠中，酮色林可将其逆转为心动过缓。由于即使在对数据进行标准化以补偿基线压力差异后这些差异仍然存在，因此认为酮色林对HR反射的影响是年龄依赖性的，而哌唑嗪则不是。尽管潜在机制尚不清楚，但酮色林而非哌唑嗪能选择性增强老年大鼠的反射性心动过缓并逆转反射性心动过速，这可以解释为什么对酮色林的降压反应会随年龄增加，而对哌唑嗪的降压反应则不会。
