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

Imre Pávó, Ferenc László, Éva Morschl, János Nemcsik, Anikó Berkó, David A. Cox, Ferenc A. László

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Administration of graded doses of [Arg8]vasopressin (0.06-0.18 μg 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 17β-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 17β-oestradiol or the selective oestrogen-receptor modulator raloxifene.

Original languageEnglish
Pages (from-to)101-104
Number of pages4
JournalEuropean Journal of Pharmacology
Volume410
Issue number1
DOIs
Publication statusPublished - Dec 20 2000

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Keywords

  • Blood pressure
  • Enzyme regulation
  • Nitric oxide (NO)
  • Oestrogen
  • Oestrogen receptor modulator
  • Vasopressin

ASJC Scopus subject areas

  • Pharmacology

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