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(Stroke. 2003;34:2038.)
© 2003 American Heart Association, Inc.

Original Contributions

Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles

From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City.

Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, E315-GH, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1081. E-mail frank-faraci{at}uiowa.edu

Background and Purpose— Angiotensin II (Ang II) produces oxidative stress in vascular cells in culture and in extracranial conduit arteries. The goal of this study was to examine the hypothesis that Ang II produces superoxide-mediated impairment of endothelial function in cerebral microvessels.

Methods— Diameter of cerebral arterioles (baseline diameter=104±3 µm) was measured with the use of a closed cranial window in anesthetized rabbits. Topical application of Ang II was used to avoid effects on arterial pressure.

Results— Ang II (0.1 to 1 µmol/L for 2 hours) had no effect on baseline diameter (change in diameter of -3±2% in response to 1 µmol/L Ang II) but produced concentration-dependent inhibition of vasodilatation to the endothelium-dependent agonist bradykinin. For example, 1 µmol/L Ang II inhibited responses to 1 nmol/L bradykinin by almost 80%. These inhibitory effects of Ang II were prevented by the superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron; 10 mmol/L) or diphenylene iodonium (DPI; 3 µmol/L), an inhibitor of NAD(P)H oxidase. Ang II did not inhibit vasodilatation in response to nitroprusside, an endothelium-independent vasodilator.

Conclusions— These findings are the first evidence that local Ang II produces superoxide-mediated vascular dysfunction in cerebral microvessels. The results with DPI suggest that the source of superoxide may be an NAD(P)H oxidase.

Key Words: bradykinin • cerebral circulation • endothelium • reactive oxygen species • rabbits

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