engleski

Low-dose angiotensin II supplementation restores flow-induced dilation mechanisms in cerebral arteries of Sprague-Dawley rats on a high salt diet

Objective: Salt-induced suppression of angiotensin II contributes to impaired endothelium-dependent vascular reactivity. The present study investigated the effect of chronic low-dose angiotensin II (ANG II) supplementation on the mechanisms of flow-induced dilation (FID) and oxidative stress at the cellular and molecular level in middle cerebral arteries (MCA) of male Sprague-Dawley rats fed high salt (HS) diet. Methods: Rats (10 weeks old) were randomly assigned to a: low salt diet group (LS, 0.4% NaCl in rat chow) ; HS group (7 days 4% NaCl in rat chow) or HS+ANG II group (7 days HS diet with 3 days ANG II administration via osmotic minipumps (100 ng/kg/min. on days 4-7)). FID was determined in absence/presence of the NOS inhibitor L-NAME, the non-selective cyclooxygenase (COX-1, 2) inhibitor indomethacin, a selective inhibitor of CYP450 epoxygenase activity (MS-PPOH) and the superoxide dismutase mimetic TEMPOL. Gene expression of antioxidative enzymes, and of genes and proteins involved in FID mechanisms were determined by RT-qPCR and Western blot. Vascular NO and superoxide/ROS levels were assessed by direct fluorescence. Serum systemic oxidative stress parameters were measured by spectrophotometry. Results: Chronic low-dose ANG II supplementation in HS-fed rats restored FID of MCAs which was nitric oxide-, prostanoid-, and epoxyeicosatrienoic acid-dependent. ANG II changed the protein/gene expression of COXs, HIF-1α and VEGF and significantly increased GPx4 and EC-SOD antioxidative enzyme expression, decreased systemic oxidative stress, decreased superoxide/ROS levels and increased NO bioavailability in the vascular wall. Conclusions: Physiological levels of circulating ANG II are crucial to maintain the HIF-1 dependent mechanisms of FID and vascular oxidative balance without affecting mean arterial pressure.

angiotensin II ; flow-induced dilation ; high salt diet ; middle cerebral arteries ; oxidative stress

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