Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca super(2+) 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 a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca super(2+) ([Ca super(2+)] sub(i)) in response to methacholine (10 mu M) and histamine (10 mu M) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 mu M)-induced increases in [Ca super(2+)] sub(i) were unaffected. Methacholine-induced nitric oxide (NO) production was eliminated in endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5 ng times kg super(-1) times min super(-1) iv) for 3 days prevented impaired [Ca super(2+)] sub(i) signaling response to methacholine and histamine and restored methacholine-induced NO production in aortas from rats on a HS diet. Adding Tempol (500 mu M) to the tissue bath to scavenge superoxide anions increased NO release and caused N omega -nitro-L-arginine methyl ester-sensitive vascular relaxation in aortas from rats fed a HS diet but had no effect on methacholine-induced Ca super(2+) responses. Chronic treatment with Tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased methacholine-induced Ca super(2+) responses significantly in aortas from rats on a HS diet but not in aortas from rats on a LS diet. These findings suggest that 1) agonist-induced Ca super(2+) responses and NO levels are reduced in aortas of rats on a HS diet; 2) increased vascular superoxide levels contribute to NO destruction, and, eventually, to impaired Ca super(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 super(2+) signaling, and reduced NO production in the endothelium.