Cerebral vascular effects of angiotensin II: new insights from genetic models
Cerebral vascular effects of angiotensin II: new insights from genetic models
复制标题
DOI：
10.1038/sj.jcbfm.9600204
复制
发表时间：
2006-04-01
影响因子：
6.3
通讯作者：
Didion, SP
中科院分区：
文献类型：
--
作者：
Faraci, FM;Lamping, KG;Didion, SP
关于血管紧张素II（Ang II）的作用机制或脑循环中Ang II依赖性高血压的后果知之甚少。我们验证了血管紧张素II通过激活AT（1A）受体和Rho激酶介导的脑动脉收缩的假设。分离小鼠的基底动脉（基线直径类似于130 μ m），插管并加压以测量血管直径。血管紧张素II是一种有效的收缩剂，在动脉从男性，但不是女性，小鼠。在对照小鼠中，Rho激酶抑制剂（Y-27632）可阻止血管紧张素II引起的血管收缩，在AT（1A）受体表达缺陷的小鼠中，血管收缩减少了约85%。我们还使用血管紧张素II依赖性高血压模型，即过度表达人肾素（R+）和血管紧张素原（A（+））的小鼠，研究了血管紧张素II的慢性效应。R（+）A（+）小鼠对内皮依赖性激动剂乙酰胆碱的反应明显受损（P
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