BACKGROUND AND OBJECTIVES: It has been suggested that nitric oxide (NO) and atrial natriuretic peptide (ANP) share a final common pathway for vascular smooth muscle relaxation. The aim of the present study was to determine the role of NO on the hypotensive and vasorelaxant effects of ANP. MATERIALS AND METHODS: Sprague-Dawley rats weighing 250-300 g each were anesthetized with thiopental (50 mg/kg IP). The femoral artery was cannulated and the arterial blood pressure and heart rate were continuously monitored in the anesthetized rats (n=19). ANP was administered into the jugular vein after L-NAME treatment. In vitro experiments were performed on intact and endothelium-denuded isolated thoracic aortic rings (n=51) in the presence of either L-NAME or methylene blue. RESULTS: Intravenous administration of ANP (5 ug/kg bolus and 0.2 ug/kg/min infusion) caused a decrease in the mean arterial pressure. L-NAME-pretreatment (1 mg/kg) suppressed the depressor response of ANP. In vitro, the ANP caused a dose-dependent relaxation, and the relaxation response to ANP was attenuated by L-NAME (10-4 M). Endothelium removal or methylene blue (10-5 M) also inhibited the ANP-induced vascular relaxation. CONCLUSION: These results suggest that the hypotensive and the vasorelaxant effect of ANP are, at least in part, NO-dependent.