Hyperinsulinemia and high salt intake represent two independent cardiovascular risk factors. However, it is still unknown whether the change in dietary salt intake may affect the ability of insulin to stimulate whole-body glucose uptake and to modulate endothelial function. Regarding this latter issue, we have recently demonstrated that insulin enhances endothelial-mediated alpha2-adrenergic vasorelaxation. In overnight-fasted, freely moving Wistar-Kyoto rats (10 to 12 weeks old), we assessed whole-body glucose uptake (in milligrams per kilogram per minute) during a euglycemic-hyperinsulinemic clamp (insulin infusion rate, 3 mU x kg(-1) x min(-1)) after 3 weeks of normal (NSD, 2% NaCl), high (HSD, 6% NaCl), and low (LSD, 0.6% NaCl) sodium diet. Three days after the clamp study, rats were killed to assess alpha2-adrenergic vasorelaxation evoked by UK 14,304 (10(-9) to 10(-6) mol/L) in aortic rings in control conditions and after insulin exposure (100 microU/mL). Different sodium intakes did not modify the mean blood pressure or the insulin-stimulated whole-body glucose uptake (NSD: 14+/-1.2, n=16; HSD: 15.4+/-1.7, n=14; LSD: 14.8+/-0.8, n=14; NS). In contrast, we confirmed the ability of insulin to enhance alpha2-adrenergic vasorelaxation during NSD and HSD (delta% of maximal relaxation, NSD: from 32+/-3% to 58+/-3.4%, n=9, P<0.01; HSD: from 33+/-3.8% to 59+/-3.5%, n=8, P<0.01), but this effect was impaired during LSD (delta% maximal relaxation, from 36+/-1.5% to 36+/-3.4%, n=8, NS). In conclusion, our data demonstrate that in Wistar-Kyoto rats, changes in dietary salt intake do not modify the insulin-stimulated whole-body glucose uptake. In contrast, LSD impairs the insulin potentiation of alpha2-adrenergic vasorelaxation, thus suggesting that dietary salt restriction provokes an impairment of insulin effect on endothelial function.