Involvement of natriuretic hormones and Na+ transport in the antihypertensive action of canrenone.
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.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002192:Canrenone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D045283:Natriuretic Agents / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D011245:Pregnadienes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood / Q000378:metabolism*
D000959:Antihypertensive Agents; D007473:Ion Channels; D045283:Natriuretic Agents; D011245:Pregnadienes; D010042:Ouabain; D002192:Canrenone; D012964:Sodium; D011188:Potassium; D002118:Calcium