title: Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats.
abstract: 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.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Yun-Gang
authors.initials: YG
authors.lastname: Bai
authors.forename: Le-Jian
authors.initials: LJ
authors.lastname: Lin
authors.forename: Jun-Xiang
authors.initials: JX
authors.lastname: Bao
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Jiu-Hua
authors.initials: JH
authors.lastname: Cheng
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Jia
authors.forename: Xin-Ling
authors.initials: XL
authors.lastname: Ren
authors.forename: Jin
authors.initials: J
authors.lastname: Ma
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000378:metabolism; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019417:Hindlimb Suspension; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D018474:Weightlessness Simulation
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019808:Losartan