Raloxifene, an oestrogen-receptor modulator, prevents decreased constitutive nitric oxide and vasoconstriction in ovariectomized rats

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 ovari ectomized female rat, with the elevation of blood pressure more marked foll owing ovariectomy. In addition, ovariectomy caused the down-regulation of a ortic Ca2+-dependent constitutive nitric oxide synthase (assessed by the ci trulline assay). The down-regulation of the Ca2+-dependent constitutive nit ric oxide synthase and augmentation of vasopressin-induced blood pressure r esponses were prevented by the therapy (1 month, p.o.) with the selective o estrogen receptor modulator, raloxifene (0.3-1.0 mg kg(-1) day(-1)), or wit h 17 beta -oestradiol (0.3 mg kg(-1) day(-1)) in ovariectomized rats. Thus, oestrogen deficiency down-regulates vascular constitutive nitric oxide syn thase, which appears to be involved in the increased sensitivity of the vas culature to vasopressin, since both effects can be reversed by the exogenou s administration of the natural oestrogen 17 beta -oestradiol or the select ive oestrogen-receptor modulator raloxifene. (C) 2000 Elsevier Science B.V. All rights reserved.