Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats

Autor: Ran Zhang, Jiu-Hua Cheng, Hao Tang, Yun-Gang Bai, Xinling Ren, Jun-Xiang Bao, Guo-Liang Jia, Le-Jian Lin, Yu-Yang Zhang, Jin Ma
Rok vydání: 2009
Předmět:
Male
medicine.medical_specialty
Nitric Oxide Synthase Type III
Carotid Artery
Common
Physiology
Vasodilator Agents
Carotid arteries
Nitric Oxide Synthase Type II
Hindlimb
medicine.disease_cause
Losartan
Receptor
Angiotensin
Type 1
Rats
Sprague-Dawley
Renin-Angiotensin System
chemistry.chemical_compound
Superoxides
Physiology (medical)
Internal medicine
Animals
Vasoconstrictor Agents
Medicine
Weightlessness Simulation
Angiotensin II receptor type 1
Dose-Response Relationship
Drug
biology
business.industry
Superoxide
Angiotensin II
Anatomy
Rats
Blockade
Vasodilation
Nitric oxide synthase
Oxidative Stress
Endocrinology
Hindlimb Suspension
chemistry
Vasoconstriction
Basilar Artery
Models
Animal
biology.protein
Nitric Oxide Synthase
business
Angiotensin II Type 1 Receptor Blockers
Oxidative stress
Zdroj: Journal of Applied Physiology. 106:251-258
ISSN: 1522-1601
8750-7587
DOI: 10.1152/japplphysiol.01278.2007
Popis: 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 (AT1) receptors with losartan on vascular reactivity, nitric oxide synthase (NOS) expression, and superoxide anion (O2•−) 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 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 ( 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 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 an ANG II/AT1 receptor signaling pathway.
Databáze: OpenAIRE
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