Involvement of Natriuretic Hormones and Na⁺ Transport in the Antihypertensive Action of Canrenone

Abstract

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, (iij secretion of natriuretic factors, (in) abnormal cell 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.