Regulation of bradykinin B 2-receptor expression by oestrogen

Paolo Madeddu, Costanza Emanueli, Maria Vittoria Varoni, Maria Piera Demontis, Vittorio Anania, Nicola Gorioso, Julie Chao

Research output: Contribution to journalArticlepeer-review

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 B 2-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 B 2-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(-l)), desArg 9-bradykinin (150-900 ng kg -1) or prostaglandin E 2 (30-600 ng kg -1) were significantly reduced by ovariectomy. Oestrogen restored to normal the responses to desArg 9-bradykinin, acetylcholine and prostaglandin E 2, but not that to sodium nitroprusside. 4 B 2-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 B 2-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.

Original languageEnglish
Pages (from-to)1763-1769
Number of pages7
JournalBritish Journal of Pharmacology
Volume121
Issue number8
DOIs
Publication statusPublished - 1997

Keywords

  • Blood pressure
  • Bradykinin
  • Bradykinin B receptors
  • mRNA
  • Oestrogen
  • Ovariectomy
  • Vasodilatation

ASJC Scopus subject areas

  • Pharmacology

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