Grichois M L, de Mendonça M, Wauquier I, Pernollet M G, Thormann B, Devynck M A, Meyer P, Garay R P
Arch Mal Coeur Vaiss. 1986 Jun;79(6):875-8.
Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension results from a transient and chronic "cascade" of events; I) excess Na+ intake, II) secretion of natriuretic factors, III) abnormal cell Na+ homeostasis in the vascular wall, due to the presence of inherited and induced abnormalities in different Na+ transport system and IV) increase in cytosolic free Ca2+ content and sympathetic drive. In vitro studies have previously shown that canrenone, an antihypertensive antialdosterone drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+-pump. In particular, it has been shown that canrenone counterbalances the increases in internal Na+ and cytosolic free Ca2+ contents induced by ouabain in cultured smooth muscle cells. We thus investigated the effect of canrenone administration in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass under excess Na+ intake: RRM-salt rats). Results presented here confirm that RRM-salt rats exhibit: volume expansion, strongly decreased plasma renin activity, increased endogenous "ouabain-like" factors and (IV) decreased Na+, K+-pump activity and increased Na+ content in erythrocytes. In addition, we found that canrenone is antihypertensive in this model and this is associated with a tendency to normalize volume expansion, plasma levels of endogenous "ouabain-like" factors, Na+, K+-pump activity and Na+ content in erythrocytes. In conclusion, our results suggest that administration of canrenone to RRM-salt rats may induce a lowering of blood pressure by antagonism with endogenous "ouabain-like" factors at the vascular wall.
近期针对原发性高血压患者以及遗传性高血压大鼠的研究有力地表明，原发性高血压的发展源于一系列短暂且慢性的“级联”事件：I）钠摄入过量；II）利钠因子分泌；III）血管壁细胞钠稳态异常，这是由于不同钠转运系统中存在遗传性和诱导性异常所致；IV）胞质游离钙含量增加以及交感神经驱动增强。此前的体外研究表明，抗高血压抗醛固酮药物坎利酮在钠钾泵的洋地黄受体位点表现为部分激动剂。具体而言，已证实坎利酮可抵消哇巴因在培养的平滑肌细胞中诱导的细胞内钠和胞质游离钙含量的增加。因此，我们研究了在具有内源性“类哇巴因”因子增加的实验性高血压模型（高钠摄入下肾质量减少的大鼠：RRM - 盐大鼠）中给予坎利酮的效果。此处呈现的结果证实，RRM - 盐大鼠表现出：容量扩张、血浆肾素活性大幅降低、内源性“类哇巴因”因子增加以及（IV）钠钾泵活性降低和红细胞内钠含量增加。此外，我们发现坎利酮在该模型中具有降压作用，这与容量扩张、内源性“类哇巴因”因子血浆水平、钠钾泵活性以及红细胞内钠含量趋于正常化有关。总之，我们的结果表明，给RRM - 盐大鼠施用坎利酮可能通过在血管壁与内源性“类哇巴因”因子拮抗而导致血压降低。
