A lower ratio of AT1/AT2 receptors of angiotensin II is found in female than in male spontaneously hypertensive rats.
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 II vascular reactivity and AT(1) and AT(2) 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, AT(1) and AT(2) 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 AT(1) was higher in aorta and mesenteric vessels from males than in females. In ovariectomized SHR, mRNA expression for AT(1) was comparable to that of males. Treatment with estrogen reversed the over expression observed. Whereas AT(2) gene expression did not differ, a lower ratio AT(1)/AT(2) was found in female than in male vessels. A higher mRNA expression for AT(1) was observed in kidney from male than in female. Ovariectomy resulted in up-regulation of this subtype receptor. Treatment with estrogen reversed the overexpression. AT(2) gene expression was higher in kidney from female than male SHR. Ovariectomy reduced AT(2) gene expression and estrogen treatment reversed the alteration observed in kidney.


CONCLUSIONS
There is sexual dimorphism in vascular reactivity and in receptor gene expression to Ang II in SHR. We conclude that estrogen modulates AT(1) and AT(2) receptor gene expression and that this might explain at least partially the lower blood pressure observed in female SHR.
Silva-Antonialli
Michele Melo
MM
Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900, Av. Prof. Lineu Prestes, 1524-Sao Paulo, SP, Brazil.
Tostes
Rita C A
RC
Fernandes
Lílian
L
Fior-Chadi
Débora Rejane
DR
Akamine
Eliana Hiromi
EH
Carvalho
Maria Helena C
MH
Fortes
Zuleica Bruno
ZB
Nigro
Dorothy
D
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology; D004971:Estrus / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000737:chemistry*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis* / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D014655:Vascular Resistance / Q000187:drug effects
D004967:Estrogens; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II