Published Online
on February 14, 2005

A more recent version of this article appeared on April 1, 2005

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Submitted on October 7, 2004
Revised on November 4, 2004

Reduced Angiotensin II and Oxidative Stress Contribute to Impaired Vasodilation in Dahl Salt-Sensitive Rats on Low-Salt Diet

Ines Drenjancevic-Peric and Julian H. Lombard^*

From the Department of Physiology, Medical College of Wisconsin, Milwaukee.

^* To whom correspondence should be addressed. E-mail: jlombard{at}mcw.edu.

Abstract--This study investigated the role of impaired angiotensin II (Ang II) modulation in contributing to reduced vascular relaxation in isolated middle cerebral arteries (MCA) (100 to 200 µm in diameter) of normotensive Dahl salt-sensitive (SS) rats maintained on low salt (LS) diet (0.4% NaCl) for 9 to 10 weeks. MCA from SS rats on LS diet (n=6 to 9) constricted in response to reduction of perfusate and superfusate PO₂ to 35 to 40 mm Hg or acetylcholine (ACh). Vasodilator responses to reduced PO₂ and ACh were restored in SS.13^BN consomic rats that are 98% genetically identical to SS rats, but exhibit normal regulation of their renin-angiotensin system (RAS). This restored dilation could be prevented by feeding SS.13^BN rats high-salt (HS) diet (4% NaCl) for 3 days to suppress Ang II. A continuous intravenous infusion of a subpressor dose (3 ng/kg per minute) of Ang II for 3 days restored vasodilator responses to ACh and reduced PO₂ in SS.13^BN rats on HS diet and in SS rats on LS diet. Superoxide scavenging with tempol (100 µmol/L) restored vasodilator responses to ACh and reduced PO₂ in MCA of SS rats on LS diet, but did not affect vasodilator responses in MCA of SS.13^BN rats on LS diet. These data indicate that exposure to chronically low Ang II levels leads to impaired vascular relaxation in SS rats, even when the animals are on LS diet and normotensive. This impaired relaxation appears to be mediated by increased levels of oxidative stress in the arteries.

Key words: angiotensin II • endothelium • muscle, smooth, vascular • oxygen • vasodilation

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