Submitted on December 4, 2007
Accepted on November 5, 2008
Blockade of AT1 Receptor Partially Restores Vasoreactivity, NOS Expression and Superoxide Levels in Cerebral and Carotid Arteries of Hindlimb Unweighting Rats
Ran Zhang1, Yun-Gang Bai2, Le-Jian Lin2, Jun-Xiang Bao3, Yu-Yang Zhang4, Hao Tang2, Jiu-Hua Cheng5, Guo-Liang Jia6, Xin-Ling Ren7, and Jin Ma3*
1 Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China; Department Of Aerospace Physiology, Fourth Military Medical University, Xi'an, Shaanxi, China; Institute of Geriatric Cardiology, General Hospital of PLA, Beijing, China
2 Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, Shaanxi Province, China
3 Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, Shaanxi Provonce, China
4 Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department Of Aerospace Physiology, Fourth Military Medical University, Xi'an, Shaanxi, China
5 Department Of Aerospace Physiology, Fourth Military Medical University, Xi'an, Shaanxi, China
6 Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
7 Department of Respiratory Diseases, Xijing Hospital, Xi'an, Shaanxi, China
* To whom correspondence should be addressed. E-mail: jin-ma{at}fmmu.edu.cn.
Previous studies have demonstrated activation of local renin-angiotensin system in hindlimb unweighting (HU) rat vasculature. The present study intended to identify the effects of blockade of angiotensin II type 1 (AT1) receptors with losartan on vascular reactivity, nitric oxide synthase (NOS) expression and superoxide anions (O2·-) levels in 3-week HU rat cerebral and carotid arteries. Three weeks later, vasoconstriction, vasodilatation, endothelial NOS (eNOS) and inducible NOS (iNOS) protein as well as O2·- 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 arteries (P<0.05) from HU rats than those from controls. Chronic treatment of losartan partially restored response to vasoconstrictors and acetylcholine-induced vasodilatation in basilar (P<0.01) and common carotid arteries (P<0.05) 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 O2·- levels in all the layers of these arteries. However, losartan restored NOS content and O2·- levels toward normal. These results suggested that the HU-induced enhancement of vasoconstriction and reduction in endothelium-dependent relaxation involved alterations in O2·- and NOS content through ANGII/AT1 receptors signaling pathway.
