TY - JOUR
T1 - Regulation of bradykinin B 2-receptor expression by oestrogen
AU - Madeddu, Paolo
AU - Emanueli, Costanza
AU - Varoni, Maria Vittoria
AU - Demontis, Maria Piera
AU - Anania, Vittorio
AU - Gorioso, Nicola
AU - Chao, Julie
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Blood pressure
KW - Bradykinin
KW - Bradykinin B receptors
KW - mRNA
KW - Oestrogen
KW - Ovariectomy
KW - Vasodilatation
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U2 - 10.1038/sj.bjp.0701255
DO - 10.1038/sj.bjp.0701255
M3 - Article
C2 - 9283715
AN - SCOPUS:0030608797
VL - 121
SP - 1763
EP - 1769
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 8
ER -