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The present study evaluated the role of nitric oxide (NO) in the systemic vascular and renal adaptation to changes in dietary sodium intake.Seven healthy normotensive male subjects were randomized to high or low sodium diets in a double blind crossover design (7 days on each diet). The NO synthesis inhibitor, NGmonomethyl-L-arginine (LNMMA) was infused systemically (1.8 mg/kg over 30 min) at the end of each dietary period and its effects on blood pressure, renal plasma flow, glomerular filtration rate, urinary flow rate and sodium excretion were measured.Blood pressure increased in response to L-NMMA on a high sodium diet only (area under time curve percentage change in mean blood pressure, low sodium = −94.5 ± 164.3; high sodium = 391.1 ± 228.6; P <0.05 low versus high). The increase in blood pressure was directly and significantly associated with the individual salt sensitivity, defined by the difference in systemic mean blood pressure between high and low sodium diets (r = 0.756; P <0.05). L-NMMA also reduced renal plasma flow and urinary flow rate in subjects on high sodium diet.The data support a significant influence of endogenous NO in the systemic and renal vascular adaptation to a high sodium diet in normotensive men. In addition, the direct association between the individual sodium-sensitivity and the pressor response to L-NMMA suggests that there is increased dependence of vascular tone on NO in normotensive subjects whose blood pressure is more sodium sensitive.