Cerebral vascular effects of angiotensin II: New insights from genetic models

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Abstract

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter ∼130 μm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by ∼85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A +). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in RA mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R + A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide. © 2006 ISCBFM All rights reserved.

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Faraci, F. M., Lamping, K. G., Modrick, M. L., Ryan, M. J., Sigmund, C. D., & Didion, S. P. (2006). Cerebral vascular effects of angiotensin II: New insights from genetic models. Journal of Cerebral Blood Flow and Metabolism, 26(4), 449–455. https://doi.org/10.1038/sj.jcbfm.9600204

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