Hannaert P, de Mendonca M, Grichois M L, Nazaret C, Abitbol J P, Garay R
Uremia Invest. 1985;9(2):195-201. doi: 10.3109/08860228509088211.
Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension takes place by a transient and chronic "cascade" of events (i) excess Na+ intake, (ii) secretion of natriuretic factors, (iii) abnormal cells Na+ homeostasis in the vascular wall, due to the presence of inherited abnormalities in different Na+ transport systems, and (iv) increase in cytosolic free Ca2+ content and catecholamines. Canrenone, an antihypertensive drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+ pump. We observed here that (i) a 4 hr preincubation of human red cells with this compound increases its antagonistic properties against ouabain, (ii) in cultured smooth muscle cells, canrenone counterbalances the increase in cytosolic free Ca2+ induced by ouabain, and (iii) in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass), the administration of canrenone tends to normalize Na+, K+-pump activity and decrease blood pressure.
最近对原发性高血压患者和遗传性高血压大鼠的研究有力地表明，原发性高血压的发生是由一系列短暂和慢性的“级联”事件引起的：(i) 过量的钠摄入；(ii) 利钠因子的分泌；(iii) 由于不同钠转运系统存在遗传性异常，导致血管壁细胞钠稳态异常；(iv) 细胞质游离钙含量和儿茶酚胺增加。坎利酮是一种抗高血压药物，在钠钾泵的洋地黄受体位点表现为部分激动剂。我们在此观察到：(i) 用该化合物对人红细胞进行4小时预孵育可增强其对哇巴因的拮抗特性；(ii) 在培养的平滑肌细胞中，坎利酮可抵消哇巴因诱导的细胞质游离钙增加；(iii) 在内源性“类哇巴因”因子增加的实验性高血压模型（肾质量减少的大鼠）中，给予坎利酮倾向于使钠钾泵活性正常化并降低血压。
