© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
A lower ratio of AT1/AT2 receptors of angiotensin II is found in female than in male spontaneously hypertensive rats
aLaboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900, Av. Prof. Lineu Prestes, 1524-São Paulo, SP, Brazil
bDepartment of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, SP, Brazil
* Corresponding author. Tel./fax: +55-11-3091-7317. Email address: dorothy{at}icb.usp.br
Objective: Sexual dimorphism has been observed in arterial hypertension. Blood pressure levels are lower in female than in male spontaneously hypertensive rats (SHR). Angiotensin II (Ang II) plays a major role in the regulation of blood pressure. The aim of this study was to compare Ang IIvascular reactivity and AT1 and AT2 receptor gene expression in female and male SHR. Methods: SHR animals were divided into four groups: (I) male, (II) female in physiological estrus, (III) ovariectomized and (IV) ovariectomized treated with estrogen. Arterial blood pressure, AT1 and AT2 mRNA expression were determined. Ang II responses in aorta and mesenteric vessels were also evaluated. Results: In female SHR, aorta and mesenteric microvessels were hyporeactive to Ang II in comparison to male SHR. In ovariectomized females, Ang II vasoconstriction was similar to that of males. Estrogen treatment abolished this difference. The mRNA expression for AT1 was higher in aorta and mesenteric vessels from males than in females. In ovariectomized SHR, mRNA expression for AT1 was comparable to that of males. Treatment with estrogen reversed the over expression observed. Whereas AT2 gene expression did not differ, a lower ratio AT1/AT2 was found in female than in male vessels. A higher mRNA expression for AT1 was observed in kidney from male than in female. Ovariectomy resulted in up-regulation of this subtype receptor. Treatment with estrogen reversed the overexpression. AT2 gene expression was higher in kidney from female than male SHR. Ovariectomy reduced AT2 gene expression and estrogen treatment reversed the alteration observed in kidney. Conclusion: There is sexual dimorphism in vascular reactivity and in receptor gene expression to Ang II in SHR. We conclude that estrogen modulates AT1 and AT2 receptor gene expression and that this might explain at least partially the lower blood pressure observed in female SHR.
KEYWORDS Sexual dimorphism; Vascular reactivity; AT1 and AT2 gene expression
Time for primary review 36 days
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