期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 410, 期 1, 页码 101-104出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(00)00865-7
关键词
oestrogen receptor modulator; oestrogen; nitric oxide (NO); blood pressure; vasopressin; enzyme regulation
Administration of graded doses of [Arg(8)]vasopressin (0.06-0.18 mug kg(-1), i.v.) induced a dose-dependent increase in arterial blood pressure in the catecholamine-depleted (phentolamine; 10 mg kg(-1), i.p.) intact and ovariectomized female rat, with the elevation of blood pressure more marked following ovariectomy. In addition, ovariectomy caused the down-regulation of aortic Ca2+-dependent constitutive nitric oxide synthase (assessed by the citrulline assay). The down-regulation of the Ca2+-dependent constitutive nitric oxide synthase and augmentation of vasopressin-induced blood pressure responses were prevented by the therapy (1 month, p.o.) with the selective oestrogen receptor modulator, raloxifene (0.3-1.0 mg kg(-1) day(-1)), or with 17 beta -oestradiol (0.3 mg kg(-1) day(-1)) in ovariectomized rats. Thus, oestrogen deficiency down-regulates vascular constitutive nitric oxide synthase, which appears to be involved in the increased sensitivity of the vasculature to vasopressin, since both effects can be reversed by the exogenous administration of the natural oestrogen 17 beta -oestradiol or the selective oestrogen-receptor modulator raloxifene. (C) 2000 Elsevier Science B.V. All rights reserved.
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