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 Ca²⁺ ([Ca²⁺]_i) in response to methacholine (10 µM) and histamine (10 µM) were significantly attenuated in aortic endothelial cells from rats fed HS diet, while thapsigargin (10 µM)-induced increases in [Ca²⁺]_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^-1xmin^-1, i.v.) for 3 days prevented impaired [Ca²⁺]_i signaling response to methacholine and histamine and restored methacholine-induced NO production in aortas from rats on HS diet. Adding tempol (500 µM) 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 Ca²⁺ responses. Chronic treatment with tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased in methacholine-induced Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ signaling in the vascular endothelial cells; and 3), reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca²⁺ signaling, and reduced NO production in the endothelium.