Antihypertensive effect of canrenone in a model where endogenous ouabain-like factors are present.
The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.
D000818:Animals; D000959:Antihypertensive Agents; D001798:Blood Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002192:Canrenone / Q000494:pharmacology*; D002298:Cardenolides; D004077:Digoxin; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D011188:Potassium / Q000097:blood; D011245:Pregnadienes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012503:Saponins; D012964:Sodium / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D000959:Antihypertensive Agents; D001798:Blood Proteins; D002298:Cardenolides; D007473:Ion Channels; D011245:Pregnadienes; D012503:Saponins; C034504:digoxin-like factors; D004077:Digoxin; D002192:Canrenone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium