Reactive oxygen species may contribute to reduced endothelium-dependent dilation in rats fed high salt

In normotensive rats, an increase in dietary salt leads to decreased arteri olar responsiveness to acetylcholine (ACh) because of suppressed local nitr ic oxide (NO) activity. We evaluated the possibility that generation of rea ctive oxygen species in the arteriolar wall is responsible for this loss of NO activity. Arteriolar responses to iontophoretically applied ACh were ex amined in the superfused spinotrapezius muscle of Sprague-Dawley rats fed a low-salt (LS; 0.45%) or high-salt diet (HS; 7%) for 4-5 wk. Responses to A Ch were significantly depressed in HS rats but returned to normal in the pr esence of the oxidant scavengers superoxide dismutase + catalase or 2,2,6,6 -tetamethylpiperidine-N-oxyl (TEMPO) + catalase. Arteriolar responses to th e NO donor sodium nitroprusside were similar in HS and LS rats. Arteriolar and venular wall oxidant activity, as determined by reduction of tetranitro blue tetrazolium, was significantly greater in HS rats than in LS rats. Exp osure to TEMPO + catalase reduced microvascular oxidant levels to normal in HS rats. These data suggest that a high-salt diet leads to increased gener ation of reactive oxygen species in striated muscle microvessels, and this increased oxidative state may be responsible for decreased endothelium-depe ndent responses associated with high salt intake.