Endothelin-1 contributes to the sexual differences in renal damage in DOCA-salt rats.
We investigated whether gender differences in renal damage in DOCA-salt hypertension are associated with effects of ovarian hormones and/or endothelin-1 (ET-1). Renal injuries and renal pre-pro-ET-1 mRNA expression were enhanced in male and female ovariectomized (OVX) DOCA rats versus female DOCA rats. Treatment with estrogen plus progesterone or progesterone, but not estrogen alone, attenuated renal damage and pre-pro-ET-1 mRNA expression in OVX DOCA rats. The ETA antagonist BMS182874 greatly ameliorated renal damage in male and OVX DOCA rats. In conclusion, the ovarian hormones have a protective role on the renal structural alterations in female DOCA rats by modulating effects of ET-1, via ETA receptors.
Montezano
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Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Av. Lineu Prestes, 1524 Sao Paulo, SP 05508-900, Brazil.
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D000818:Animals; D003619:Dansyl Compounds / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000037:antagonists & inhibitors / Q000737:chemistry; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D010052:Ovariectomy / Q000379:methods; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000187:drug effects; D012727:Sex Characteristics; D012965:Sodium Chloride
D003619:Dansyl Compounds; D019332:Endothelin-1; D004967:Estrogens; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; C085754:5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide; D006830:Hydralazine; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D011374:Progesterone