Nitric oxide produced by endothelial cells is a mediator involved in the regulation of vascular tone. Indeed, in vitro inhibition of basal nitric oxide release increase responses to vasoconstrictor agents, and in vivo, the parenteral or dietary administration of nitric oxide inhibitors produces an increase in blood pressure. However, the correlation of nitric oxide production and basal blood pressure in normotensive subjects is still unclear. In this study, we showed that administration, in urethane-anesthetized Wistar rat, of two inhibitors of nitric oxide synthase, such as NG-nitro-L-arginine methyl ester and methylguanidine, produced a significant increase in mean arterial blood pressure that was inversely related to basal mean arterial blood pressure at all doses tested. On the other hand, the increase in mean arterial blood pressure induced by infusion of angiotensin II did not correlate with basal mean arterial blood pressure. The pretreatment of rats with hexamethonium did not change the results observed in normal rats, ruling out an involvement of sympathetic nervous system. In conclusion, this study further confirms the presence of a tonic amount of nitric oxide, produced by endothelial cells in the bloodstream, which plays a key role in the regulation of basal blood pressure, and its reduction or inhibition may be the main cause of certain pathologic conditions characterized by high levels of blood pressure.