Our recent studies have indicated that severe salt restriction aggravates vascular insulin resistance in younger normotensive and hypertensive subjects. However, whether the extent of dietary salt restriction commonly advocated adversely affects vascular insulin resistance is unknown. To determine whether moderate dietary salt restriction might affect vascular and systemic sensitivity to insulin, we studied eight subjects after 1 week of a normal sodium diet (235 mEq/day) and 1 week of a moderate salt restriction (75 meq/day). Systemic insulin resistance as assessed by the fasting plasma glucose-to-insulin ratio was aggravated by dietary sodium restriction (normal sodium: 1.2 +/- 0.1 mmol/mIU; low sodium 0.6 +/- 0.1, P < .05). Salt restriction significantly reduced maximal insulin-mediated vasodilation (normal sodium: 51% +/- 5% of maximum nitroglycerin-mediated response; low sodium: 28% +/- 6%, P < .01). In contrast, no alterations in nitroglycerin-mediated vasodilation nor phenylephrine-mediated vasoconstriction were noted. These studies demonstrate that moderate salt restriction aggravates both systemic and vascular insulin resistance. This impairment of the vasodilating effect of insulin could be a factor attenuating the blood pressure lowering effect of a low sodium diet.