The rabbit isolated lateral saphenous vein (RLSV) has a heterogeneous population of alpha-adrenoceptors. Responses to electrical field stimulation, in the presence of cocaine, exhibit both alpha 1- and alpha 2-adrenoceptor-mediated components. The present study examined sympathetic neuroeffector transmission and the response to exogenous catecholamines after inhibition of nitric oxide (NO) synthesis with N omega-nitro-L-arginine methyl ester (L-NAME). A comparison of the response in the presence and absence of a functional endothelium was also carried out. L-NAME potentiated the first and second components of the response to nerve stimulation on the order of 300 and 500%, respectively. L-NAME also significantly potentiated responses to norepinephrine (NE), phenylephrine (PE), and UK 14304. Selective antagonism of the first phase was seen with prazosin (alpha 1-antagonist, 0.1 microM) and the second phase with rauwolscine (alpha 2-antagonist, 1 microM). In the presence of L-NAME, the remaining (uninhibited) components were potentiated. Removal of endothelial function induced by gentle rubbing of the intimal surface abolished potentiation to exogenous NE, PE, and UK14304 by L-NAME. However, a significant degree of potentiation of the neurogenic response was observed in the rubbed tissues in response to L-NAME. This suggests that there may be a nonendothelial source of NO that can modulate the neurogenic response to electrical field stimulation.