[Canrenone: an effective antihypertensive in an experimental model of hypertension in which the active transport of sodium is diminished].
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.
D000818:Animals; D000959:Antihypertensive Agents; D002192:Canrenone / Q000627:therapeutic use*; D002463:Cell Membrane Permeability; D003404:Creatinine / Q000097:blood; D004231:Diuresis; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009318:Natriuresis; D010042:Ouabain / Q000097:blood / Q000378:metabolism; D011245:Pregnadienes / Q000627:therapeutic use*; D051381:Rats; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*; D014508:Urea / Q000097:blood
D000959:Antihypertensive Agents; D011245:Pregnadienes; D010042:Ouabain; D002192:Canrenone; D014508:Urea; D012964:Sodium; D003404:Creatinine; D012083:Renin
La canrénone: un antihypertenseur efficace dans un modèle expérimental d'hypertension où le transport actif du sodium est diminué.