Faculty Collaboration Database

Cerebral vascular effects of angiotensin II: new insights from genetic models. J Cereb Blood Flow Metab 2006 Apr;26(4):449-55

Date

08/12/2005

Pubmed ID

16094317

DOI

10.1038/sj.jcbfm.9600204

Scopus ID

2-s2.0-33645849538 (requires institutional sign-in at Scopus site)   85 Citations

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 approximately 130 microm) 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 approximately 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 R+A+ 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.

Author List

Faraci FM, Lamping KG, Modrick ML, Ryan MJ, Sigmund CD, Didion SP

Author

Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Angiotensinogen
Animals
Cerebral Arteries
Cerebrovascular Circulation
Endothelium, Vascular
Female
Humans
Hypertension
Intracellular Signaling Peptides and Proteins
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Receptor, Angiotensin, Type 1
Renin
Sex Factors
Superoxides
Vasoconstriction
rho-Associated Kinases