We previously demonstrated that platelet-activating factor (PAF) when injected intravenously decreases renal sympathetic nerve activity in anesthetized dogs. Recently, nitric oxide (NO) has been shown to inhibit renal sympathetic nerve activity. The present study was designed to determine, using the NO synthase inhibitorNG-nitro-L-arginine methyl ester (L-NAME), whether endogenous NO contributes to the PAF-induced renal sympathoinhibition in anesthetized dogs. We also determined the role of NO in systemic and pulmonary hemodynamics during PAF-induced hypotension. In response to PAF (10 μg · kg−1, intravenously), renal sympathetic nerve activity showed similar responses in animals pretreated with L-NAME (n = 7; 20 mg · kg−1bolus and .05 mg · kg−1· min−1), D-NAME (n = 7), and phenylephrine (n = 7), as characterized by an initial increase (230%) followed by a decrease (56%). The depressor response to PAF was also similar as early as 10 min after injection in all PAF-injected groups. In contrast, L-NAME pretreatment potentiated PAF-induced pulmonary hypertension. Pulmonary arterial pressure 10 min after PAF in the L-NAME group (25 ± 2 mmHg) was significantly greater than that in the D-NAME group (12 ± 3 mmHg). In conclusion, endogenously produced NO is not involved in PAF-induced renal sympathetic nerve response or hypotension but attenuates PAF-induced pulmonary hypertension at the early stage in anesthetized dogs.