Enhanced ouabain sensitivity of the heart and myocardial sodium pump in aged rats.
Enhanced ouabain sensitivity of the heart and myocardial sodium pump in aged rats.
复制标题
增强老年大鼠心脏和心肌钠泵的哇巴因敏感性。
DOI：
10.1016/0014-2999(84)90652-6
复制
发表时间：
1984
影响因子：
5
通讯作者：
Kennedy,RH
中科院分区：
文献类型：
--
作者：
Katano,Y;Akera,T;Temma,K;Kennedy,RH
随着年龄的增长，对洋地黄类药物促炎作用的耐受性降低。为了确定老年心肌是否具有降低的糖苷耐受性，在年轻（3个月）、成年（8个月）和老年（26个月大）的Fisher 344大鼠中检查了哇巴因敏感性和相关的生化变化，因为年龄相关的生理和生化变化在该品系大鼠中得到了很好的表征。虽然大鼠对洋地黄具有独特的耐受性，但洋地黄的变力和毒性作用的基本机制与其他物种没有什么不同。在老年麻醉大鼠中，静脉输注哇巴因在较低剂量下产生心律失常和心脏骤停。老年心肌Na，K-ATP酶活性降低，[3 H]哇巴因结合位点减少。哇巴因结合位点的Na，K-ATP酶的亲和力没有改变。尽管有这些发现，钠泵活性，估计从哇巴因敏感的86 Rb+摄取心室肌切片，是较高的老年心肌时，观察到的摄取哇巴因的情况下，更敏感的抑制作用的糖苷。Na，K-ATP酶和钠泵数据的差异可能是由于老年心肌中钠漏内流增加所致。钠泵部位减少和哇巴因敏感性增强可能是老年心脏对洋地黄毒性耐受性降低的原因。
Tolerance to arrhythmogenic actions of digitalis decreases with advanced age. To determine if aged myocardium has reduced glycoside tolerance, ouabain sensitivity and associated biochemical changes were examined in young (3-month), adult (8-month) and aged (26-month old) Fisher 344 rats, because age-related changes in physiology and biochemistry are well characterized in this strain of rats. Although rat are uniquely tolerant to digitalis, basic mechanisms leading to inotropic and toxic actions of digitalis are not different from other species. In aged anesthetized rats, intravenous infusion of ouabain produced arrhythmias and cardiac arrest at lower doses. Aged myocardium had lower Na,K-ATPase activity and fewer high affinity [3H]ouabain binding sites. Affinity of the ouabain binding sites on Na,K-ATPase was not altered. Despite these findings, sodium pump activity, estimated from the ouabain-sensitive86Rb+uptake by ventricular muscle slices, was higher in the aged myocardium when the uptake was observed in the absence of ouabain and was more sensitive to inhibitory action of the glycoside. Differences in Na,K-ATPase and sodium pump data may be explained if sodium leak influx is increased in aged myocardium. Fewer sodium pumping sites and enhanced ouabain sensitivity of the sodium pump seem to be responsible for the reduced tolerance of aged heart to digitalis-induced toxicity.