Published Online
on July 15, 2004

A more recent version of this article appeared on September 1, 2004

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Submitted on March 18, 2004
Revised on May 19, 2004
Accepted on June 4, 2004

Evidence That Estrogen Suppresses Rho-Kinase Function in the Cerebral Circulation In Vivo

Sophocles Chrissobolis PhD; Klaudia Budzyn BSc (Hons); Philip D. Marley PhD; and Christopher G. Sobey PhD^*

From the Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.

^* To whom correspondence should be addressed. E-mail: cgsobey{at}unimelb.edu.au.

Background and Purpose--Premenopausal women are less susceptible to cardiovascular diseases than men or postmenopausal women. Such disease states are often associated with increased vascular RhoA/Rho-kinase activity and decreased activity of nitric oxide (NO). This study tested whether female gender is associated with lower Rho-kinase activity or higher NO activity in cerebral arteries in vivo and whether estrogen contributes to any such gender differences.

Methods--Changes in basilar artery diameter were measured with the use of a cranial window preparation in anesthetized Sprague-Dawley rats. Some female rats were ovariectomized (OVX) and treated subcutaneously daily for 14 days with vehicle (dimethyl sulfoxide) or 17-estradiol. Vascular expression of RhoA or Rho-kinase was assessed by Western blotting.

Results--The Rho-kinase inhibitor Y-27632 was selectively 3-fold more potent as a cerebral vasodilator in males versus females. Expression of total RhoA or Rho-kinase did not differ between males and females. In OVX rats, vasodilator responses to Y-27632 resembled responses in males. Treatment of OVX rats with 17-estradiol normalized the vasodilator effects of Y-27632 to be equivalent to responses in intact female controls. The NO synthase inhibitor N-nitro-L-arginine methyl ester caused 50% greater constriction of the basilar artery in females versus males, but responses in OVX rats treated with either vehicle or 17-estradiol did not differ from those recorded in intact females.

Conclusions--These data indicate that vascular Rho-kinase function is suppressed in females because of the effects of estrogen, whereas the higher NO activity in females is estrogen independent.

Key words: cerebral arteries • estrogens • gender • nitric oxide

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