Hypotensive action of canrenone in a model of hypertension where ouabain-like factors are present.
It has been proposed that peripheral resistance can be increased by ouabain-like factors that are able to increase cell sodium and thereby cell calcium. Canrenone has been reported to be a partial agonist of ouabain. The effect of canrenone was investigated in rats with reduced renal mass (RRM) showing evidence of excess circulating ouabain-like factors. Wistar rats were uninephrectomized, 30% of the other kidney was removed, and they were given a 0.8% NaCl solution to drink. Half of them received 60 mg/kg per day of canrenone orally for 26 days. In RRM, the following indices of a ouabain-like activity were found: erythrocyte Na+K(+)-pump activity was decreased by 39% (P < 0.001), sodium content increased by 12% (P < 0.01), net erythrocyte sodium extrusion in plasma decreased by 20% (P < 0.01), and plasma digoxin equivalents increased by 62% (P < 0.02). Canrenone increased the IC50 for ouabain from 1.05 to 2.16 x 10(-4) mol/l (P < 0.05) in erythrocytes. In RRM with systolic blood pressure of 165 mmHg, acute administration of canrenone decreased blood pressure by 36 mmHg. Chronic administration blunted the blood pressure rise by 12, 26 and 21 mmHg at days 5, 14 and 26, respectively (P < 0.05). Haematocrit was markedly reduced in RRM (33%) and much less when treated with canrenone (37.5%). In conclusion, in contrast with spontaneously hypertensive rats, RRM hypertension is a model where a ouabain-like factor is present and in which canrenone reduces blood pressure. The hypotensive effect of canrenone may be related to a competition with ouabain-like factors.
De Mendonca
M
M
Inserm Unité 7, Hôpital Necker, Paris, France.
Grichois
M L
ML
Pernollet
M G
MG
Thorman
B
B
Meyer
P
P
Devynck
M A
MA
Garay
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001810:Blood Volume / Q000187:drug effects; D002192:Canrenone / Q000494:pharmacology*; D002298:Cardenolides; D004077:Digoxin; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006977:Hypertension, Renal / Q000503:physiopathology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins; D012964:Sodium / Q000097:blood / Q000276:immunology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000187:drug effects
D000959:Antihypertensive Agents; D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D010042:Ouabain; D004077:Digoxin; D002192:Canrenone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase