14 August 1997, Volume 121, Issue 8, Pages 1763 – 1769

Article

Regulation of bradykinin B2-receptor expression by oestrogen Paolo Madeddu1,5, Costanza Emanueli3, Maria Vittoria Varoni2, Maria Piera Demontis2, Vittorio Anania2, Nicola Gorioso1 & Julie Chao4 1Clinica Medica, University of Sassari, Italy and National Institute of Biostructures and Biosystems, Osilo, Italy     2Clinica Farmacologia, University of Sassari, Italy     3Farmacologia, University of Ferrara, Italy     4Department of Biochemistry and Molecular Biology, University of South Carolina, Charleston, SC, U.S.A.     5Author for correspondence Present address: Clinica Medica, University of Sassari, Viale S. Pietro 8, 07100 Sassari, Italy

Keywords

bradykinin;   bradykinin B2 receptors;   blood pressure;   ovariectomy;   oestrogen;   mRNA;   vasodilatation

Abstract

1   Tissue kallikrein is overexpressed in the kidney of female rats, this sexual dimorphism being associated with a greater effect of early blockade of bradykinin B2-receptors on female blood pressure phenotype. We evaluated the effect of ovariectomy and oestradiol benzoate (50 µg 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 the expression of bradykinin B2-receptors. 2   Ovariectomy reduced the magnitude of the vasodepressor response to bradykinin and unmasked a secondary vasopressor effect. Oestrogen replacement restored the vasodepressor response to bradykinin in ovariectomized rats. 3   The vasodepressor responses to sodium nitroprusside (3 – 18 µg kg-1), acetylcholine (30 – 600 ng kg-1), desArg9-bradykinin (150 – 900 ng kg-1) or prostaglandin E2 (30 – 600 ng kg-1) were significantly reduced by ovariectomy. Oestrogen restored to normal the responses to desArg9-bradykinin, acetylcholine and prostaglandin E2, but not that to sodium nitroprusside. 4   B2-receptor mRNA levels were decreased by ovariectomy in the aorta and kidney and they were restored to normal levels by oestrogen. Neither ovariectomy nor oestradiol affected receptor expression in the heart and uterus. 5   These results indicate that oestrogen regulates B2-receptor gene expression and function. Since kinins exert a cardiovascular protective action, reduction in their vasodilator activity after menopause might contribute to the increased risk of pathological cardiovascular events. Conversely, the cardioprotective effects of oestrogen replacement might be, at least in part, mediated by activation of the kallikrein-kinin system.

Received 20 December, 96; Revised 11 April, 97; Accepted 17 April, 97

^© Macmillan Publishers Ltd 1997