期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 26, 期 4, 页码 449-455出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.jcbfm.9600204
关键词
acetylcholine; basilar artery; endothelium; genetically altered mice
资金
- NHLBI NIH HHS [HL-38901, HL-61446, HL-76421, HL-62984] Funding Source: Medline
- NIDDK NIH HHS [DK-25295] Funding Source: Medline
- NINDS NIH HHS [NS-24621] Funding Source: Medline
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 AT(1A) receptors and Rho-kinase. Basilar arteries ( baseline diameter similar to 130 mu m) 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 similar to 85% in mice deficient in expression of AT(1A) 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 AT(1A) 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.
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