Khatter J C, Navaratnam S
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Eur J Pharmacol. 1992 Jun 17;216(3):351-5. doi: 10.1016/0014-2999(92)90430-c.
In the present study, age-related alterations in cardiovascular response to Ca2+ agonist BAY K 8644 were investigated in rats. Dose response of BAY K 8644 (1-30 micrograms/kg) was studied in open chest rats by intravenous bolus administration. Maximum elevation of mean arterial pressure and (+)dp/dt of left ventricular pressure were significantly higher and the dose of BAY K 8644 required to produce half maximal response was substantially lower in 12 months old (4 micrograms/kg) than in 2 months old (10 micrograms/kg) rats. Larger doses of BAY K 8644 produced arrhythmias only in 12 months old rats, which was not totally abolished by nitroglycerine pretreatment. Perfusion of isolated rat hearts with 10(-6) M BAY K 8644 produced positive inotropic response, which was on the average 50% greater and developed much faster in 12 months old than in 2 months old rats. It is therefore concluded that the myocardial sensitivity to BAY K 8644 increases during adult maturation.
在本研究中，我们研究了大鼠心血管系统对钙离子激动剂BAY K 8644的年龄相关变化。通过静脉推注给药，在开胸大鼠中研究了BAY K 8644（1 - 30微克/千克）的剂量反应。12月龄大鼠（4微克/千克）平均动脉压和左心室压力最大上升速率（+）dp/dt的最大升高显著高于2月龄大鼠（10微克/千克），且产生半数最大反应所需的BAY K 8644剂量显著更低。大剂量的BAY K 8644仅在12月龄大鼠中引发心律失常，硝酸甘油预处理不能完全消除这种心律失常。用10^(-6) M BAY K 8644灌注离体大鼠心脏产生正性肌力反应，12月龄大鼠的反应平均比2月龄大鼠大50%，且发展更快。因此得出结论，成年成熟过程中心肌对BAY K 8644的敏感性增加。
