[Anti-angiogenic effects of aldosterone antagonists in the fibrin chamber in rats].
Spironolactone, a diuretic antagonist of aldosterone has an unexplained side effect of amenorrhea which could be due to an angiogenesis inhibition. In this study we compared the effects of spironolactone, canrenone an active metabolite of spironolactone and eplerenone a more selective mineralocorticoid antagonist in rats implanted with a fibrin gel chamber. Perforated plexiglass chambers filled with rat fibrin, spironolactone (50 microM), canrenone (100 microM), eplerenone (500 microM), DMSO (0.05%) and control were implanted into the dorsal subcutaneous space of wistar rats. After 14 days of implantation, an invasion of the fibrin gel chamber by neovascularised buds had occurred through the holes. The number of vessels in the central field and in two or three peripheral fields covering the surface of the bud, were measured for each drug tested and compared to the control. In spironolactone treated chambers, the numbers of peripheral and central vessels were significantly reduced compared to control (p < 0.001). Canrenone, eplerenone and DMSO did not reduce the number of vessels (m +/- ESM, ANOVA followed by Newman-Keuls test). Spironolactone but not canrenone, nor eplerenone inhibited vessels formation in vivo. This antiangiogenic activity appeared to be not related to the antimineralocorticoid effect of spironolactone.
Guggino
S
S
Laboratoire de recherche sur l'angiogenèse, institut de pharmacologie, faculté de médecine, université Louis-Pasteur, Service d'hypertension, maladies vasculaires et pharmacologie clinique, hôpitaux universitaires, Strasbourg.
Mechine Neuville
A
A
Weltin
D
D
Imbs
J L
JL
Stephan
D
D
D000568:Amenorrhea / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D002192:Canrenone / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000077545:Eplerenone; D005260:Female; D005337:Fibrin; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D002192:Canrenone; D005337:Fibrin