REGULATION OF BRADYKININ B-2-RECEPTOR EXPRESSION BY ESTROGEN

1 Tissue kallikrein is overexpressed in the kidney of female rats, thi s sexual dimorphism being associated with a greater effect of early bl ockade of bradykinin B-2-receptors on female blood pressure phenotype. We evaluated the effect of ovariectomy and oestradiol benzoate (50 mu g kg(-1) every two days for two weeks) on the vasodepressor response to intra-arterial injection of bradykinin (150-900 ng kg(-1)) and on t he expression of bradykinin B-2-receptors. 2 Ovariectomy reduced the m agnitude of the vasodepressor response to bradykinin and unmasked a se condary vasopressor effect. Oestrogen replacement restored the vasodep ressor response to bradykinin in ovariectomized rats. 3 The vasodepres sor responses to sodium nitroprusside (3-18 mu g kg(-1)), acetylcholin e (30-600 ng kg(-1)), desArg(9)-bradykinin (150-900 ng kg(-1)) or pros taglandin E-2 (30-600 ng kg(-1)) were significantly reduced by ovariec tomy. Oestrogen restored to normal the responses to desArg(9)-bradykin in, acetylcholine and prostaglandin E-2, but not that to sodium nitrop russide. 4 B-2-receptor mRNA levels were decreased by ovariectomy in t he aorta and kidney and they were restored to normal levels by oestrog en. Neither ovariectomy nor oestradiol affected receptor expression in the heart and uterus. 5 These results indicate that oestrogen regulat es B-2-receptor gene expression and function. Since kinins exert a car diovascular protective action, reduction in their vasodilator activity after menopause might contribute to the increased risk of pathologica l cardiovascular events. Conversely, the cardioprotective effects of o estrogen replacement might be, at least in part, mediated by activatio n of the kallikrein-kinin system.