Regulation of bradykinin B2-receptor expression by oestrogen.
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 micrograms 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 micrograms 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.
Madeddu
P
P
Clinica Medica, University of Sassari, Italy.
Emanueli
C
C
Song
Q
Q
Varoni
M V
MV
Demontis
M P
MP
Anania
V
V
Glorioso
N
N
Chao
J
J
Gorioso
N
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D012727:Sex Characteristics
D004967:Estrogens; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D011374:Progesterone; D001920:Bradykinin