Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats.
Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats.
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DOI：
10.1152/japplphysiol.01278.2007
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发表时间：
2009
影响因子：
3.3
通讯作者：
Ran Zhang;Yun-gang Bai;Le-jian Lin;J. Bao;Yu‐Yang Zhang;Hao Tang;Jiu-hua Cheng;Guoliang Jia
中科院分区：
文献类型：
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作者：
Ran Zhang;Yun-gang Bai;Le-jian Lin;J. Bao;Yu‐Yang Zhang;Hao Tang;Jiu-hua Cheng;Guoliang Jia
以往的研究表明，激活的局部肾素-血管紧张素系统在后肢失重（HU）大鼠血管。本研究旨在确定用氯沙坦阻断血管紧张素II（ANG II）1型（AT（1））受体对3周HU大鼠脑动脉和颈动脉血管反应性、一氧化氮合酶（NOS）表达和超氧阴离子（O（2）（*-））水平的影响。三周后，检测大鼠脑动脉和颈动脉的血管收缩、血管舒张、内皮型NOS（eNOS）和诱导型NOS（iNOS）蛋白以及O（2）（*-）水平。结果表明，HU可显著增强HU大鼠基底动脉对KCl/5-羟色胺的最大反应（P < 0.01）和颈总动脉对KCl/苯肾上腺素的最大反应（P < 0.05）。乙酰胆碱可引起所有动脉环的浓度依赖性舒张，但HU大鼠基底动脉（P < 0.01）和颈总动脉（P < 0.05）的舒张幅度明显小于对照组。氯沙坦慢性治疗部分恢复了氯沙坦治疗HU大鼠基底动脉（P < 0.01）和颈总动脉（P < 0.05）对血管收缩剂和乙酰胆碱诱导的血管舒张反应。HU组大鼠脑动脉iNOS含量和颈动脉eNOS/iNOS含量显著升高（P < 0.01）。同时，HU可使动脉各层的O（2）（*-）水平升高。而氯沙坦使NOS含量和O（2）（*-）水平恢复正常。上述结果提示，HU引起的血管收缩增强和内皮依赖性舒张减少与O（2）（*-）和NOS含量的改变有关，其机制可能是通过ANG Ⅱ/AT（1）受体信号通路实现的。
Previous studies have demonstrated activation of the local renin-angiotensin system in hindlimb unweighting (HU) rat vasculature. The present study intended to identify the effects of blockade of angiotensin II (ANG II) type 1 (AT(1)) receptors with losartan on vascular reactivity, nitric oxide synthase (NOS) expression, and superoxide anion (O(2)(*-)) levels in 3-wk HU rat cerebral and carotid arteries. Three weeks later, vasoconstriction, vasodilatation, endothelial NOS (eNOS) and inducible NOS (iNOS) protein, as well as O(2)(*-) levels in rat cerebral and carotid arteries were examined. We found that HU enhanced maximal response to KCl/5-hydroxytryptamine (P < 0.01) in basilar arteries and KCl/phenylephrine (P < 0.05) in common carotid arteries from HU rats. Acetylcholine induced concentration-dependent vasodilatation in all the artery rings, but with significantly smaller amplitude in basilar (P < 0.01) and common carotid (P < 0.05) arteries from HU rats than those from control rats. Chronic treatment with losartan partially restored response to vasoconstrictors and acetylcholine-induced vasodilatation in basilar (P < 0.01) and common carotid (P < 0.05) arteries from losartan-treated HU rats. Furthermore, iNOS content in cerebral arteries and eNOS/iNOS content in carotid arteries were significantly (P < 0.01) increased in HU rats. Meanwhile, HU increased O(2)(*-) levels in all the layers of these arteries. However, losartan restored NOS content and O(2)(*-) levels toward normal. These results suggested that the HU-induced enhancement of vasoconstriction and reduction in endothelium-dependent relaxation involved alterations in O(2)(*-) and NOS content through an ANG II/AT(1) receptor signaling pathway.