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 microg 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 Ca(2+)-dependent constitutive nitric oxide synthase (assessed by the citrulline assay). The down-regulation of the Ca(2+)-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 17beta-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 17beta-oestradiol or the selective oestrogen-receptor modulator raloxifene.
Pávó
I
I
Lilly Area Medical Center, Vienna, Austria.
László
F
F
Morschl
E
E
Nemcsik
J
J
Berkó
A
A
Cox
D A
DA
László
F A
FA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000172:deficiency; D005260:Female; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
D002395:Catecholamines; D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D014667:Vasopressins; D009569:Nitric Oxide; D020849:Raloxifene Hydrochloride; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester