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 2+ ([Ca 2+] i) in response to methacholine (10 μM) and histamine (10 μM) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 μM)-induced increases in [Ca 2+] 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·kg -1·min -1 iv) 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 a HS diet. Adding Tempol (500 μM) to the tissue bath to scavenge superoxide anions increased NO release and caused N ω-nitro-L-arginine methyl ester-sensitive vascular relaxation in aortas from rats fed a 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 methacholine-induced Ca 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 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 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.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - 2006|
- Dietary salt intake
- Nitric oxide
- Vascular relaxation