engleski

Role of Superoxide and Angiotensin II Suppression In Salt-Induced Changes in Endothelial Ca2+ Signaling and NO Production in Rat Aorta.

Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or changed to high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca(2+ )([Ca(2+)]i) in response to methacholine (10 microM) and histamine (10 microM) were significantly attenuated in aortic endothelial cells from rats fed HS diet, while thapsigargin (10 microM)-induced increases in [Ca(2+)]i were unaffected. Methacholine-induced NO production was eliminated in endothelial cells of aortas from rats fed HS diet. Low dose angiotensin II (ANG II) infusion (5 ngxkg(-1)xmin(-1), i.v.) for 3 days prevented impaired [Ca(2+)]i signaling response to methacholine and histamine and restored methacholine-induced NO production in aortas from rats on HS diet. Adding tempol (500 microM) to the tissue bath to scavenge superoxide anions increased NO release and caused L-NAME sensitive vascular relaxation in aortas from rats fed HS diet, but had no effect on methacholine-induced Ca(2+) responses. Chronic treatment with tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased in methacholine-induced Ca(2+) responses significantly in aortas from rats on HS diet but not in aortas from rats on LS diet. These findings suggest that: 1) agonist-induced Ca(2+) responses and NO levels are reduced in aortas of rats on HS diet ; 2) increased vascular superoxide levels contribute to NO destruction and, eventually, to impaired Ca(2+) signaling in the vascular endothelial cells ; and 3), reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca(2+) signaling, and reduced NO production in the endothelium.

supoeroxide; angiotensin II; endothelial cells; intracellular calcium

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