Blockade of AT 1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats

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.