This study examined whether disturbances in nitric oxide formation contribute to renal dysfunction in salt-sensitive essential hypertensive patients. We evaluated the effects of intravenous administration of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 23 patients with mild essential hypertension during 1 week of a low NaCl diet (50 mmol/d) followed by 1 week of a high NaCl diet (340 mmol/d). Patients were classified as salt sensitive (n=10) or salt resistant (n=13) based on salt-induced changes in their blood pressures. Salt loading increased renal vascular resistance but not renal plasma flow in salt-sensitive patients. The L-arginine-induced renovascular relaxation was significantly reduced by a high NaCl diet (renal vascular resistance: low NaCl -12.4 +/- 2.3% versus high NaCl -7.1 +/- 1.8%, P < .001) in salt-sensitive patients, whereas it was unchanged in salt-resistant patients. The increase in plasma cGMP in response to L-arginine was also reduced by a high NaCl diet in the salt-sensitive patients (low NaCl 49 +/- 7% versus high NaCl 36 +/- 8%, P < .05) but not in the salt-resistant patients (low NaCl 51 +/- 6% versus high NaCl 58 +/- 6%). These findings suggest that NaCl loading in salt-sensitive patients with mild essential hypertension reduces the ability of L-arginine to produce nitric oxide in the endothelium of the renal vasculature.