Vescovo G, Jones S M, Harding S E, Poole-Wilson P A
National Heart and Lung Institute, London, U.K.
J Mol Cell Cardiol. 1989 Oct;21(10):1047-61. doi: 10.1016/0022-2828(89)90803-1.
Rats treated with the alkaloid monocrotaline developed right ventricular hypertrophy with a left:right ventricle weight ratio of 1.35 +/- 0.10 (mean +/- s.e.m., n = 25) compared with 3.83 +/- 0.40 (n = 14) in diet-matched controls (P less than 0.001). Urine volume and sodium content were reduced and body water increased consistent with heart failure. In 10 out of 26 treated rats pleural, pericardial or peritoneal effusions were present. Urine norepinephrine content was significantly raised (P less than 0.02) but epinephrine was unchanged. Plasma norepinephrine levels were raised though not significantly. Myocytes isolated from the right ventricle had a reduced myosin Ca2+-activated ATPase (P less than 0.05) activity and a shift towards slower V2 and V3 myosin isoforms. There was no decrease in maximum contraction amplitude with calcium or isoproterenol in either left or right ventricular cells of treated rats. Right ventricular cells from treated rats showed a reduced rate of contraction in maximum isoproterenol (P less than 0.05) and a significant rightward shift in PD2 (P less than 0.05) representing a two-fold increase in EC50 for isoproterenol compared with right ventricular cells from control animals. There was no shift in EC50 for isoproterenol in left ventricle cells. In parallel experiments, myocytes isolated from both ventricles of rats treated with isoproterenol for one week showed a rightward shift of more than 50-fold in the isoproterenol concentration-response curve and a depressed response to maximum isoproterenol. In the rat monocrotaline model of right-sided cardiac hypertrophy and failure, changes in sensitivity to beta-adrenoceptor agonists are slight, and present only in the right ventricle. The lack of change in the left ventricle seems to suggest that this functional desensitisation is not a consequence of raised circulating catecholamines.
用生物碱野百合碱处理的大鼠出现右心室肥厚，左、右心室重量比为1.35±0.10（平均值±标准误，n = 25），而饮食匹配的对照组为3.83±0.40（n = 14）（P＜0.001）。尿量和钠含量减少，机体水分增加，这与心力衰竭一致。26只处理过的大鼠中有10只出现胸腔、心包或腹腔积液。尿去甲肾上腺素含量显著升高（P＜0.02），但肾上腺素未发生变化。血浆去甲肾上腺素水平升高，但无统计学意义。从右心室分离出的心肌细胞肌球蛋白Ca²⁺激活的ATP酶活性降低（P＜0.05），且向较慢的V2和V3肌球蛋白亚型转变。处理过的大鼠左、右心室细胞用钙或异丙肾上腺素刺激时，最大收缩幅度均未降低。处理过的大鼠右心室细胞在用最大剂量异丙肾上腺素刺激时收缩速率降低（P＜0.05），PD2显著右移（P＜0.05），这表明与对照动物的右心室细胞相比，异丙肾上腺素的EC50增加了两倍。左心室细胞中异丙肾上腺素的EC50没有变化。在平行实验中，用异丙肾上腺素处理一周的大鼠两心室分离出的心肌细胞，异丙肾上腺素浓度-反应曲线右移超过50倍，对最大剂量异丙肾上腺素的反应降低。在大鼠右心肥大和衰竭的野百合碱模型中，对β-肾上腺素能激动剂的敏感性变化轻微，且仅出现在右心室。左心室缺乏变化似乎表明这种功能脱敏不是循环儿茶酚胺升高的结果。
