The influence of nitric oxide on Na+,K+-ATPase activity in rat aorta was studied by means of stimulation of endogenous NO synthesis after injections of bacterial lipopolysaccharide (LPS) and pharmacological NO donor nitroglycerine (NG). It was shown that NO action on Na+,K+-ATPase in vivo is dose-de­pendent. Stimulation of the endogenous NO synthesis by LPS as well as the administration of low doses of NG lead to the activation of Na+,K+-ATPase and favor the conclusion that NO-dependent Na+,K+-ATPase stimulation mediates vasodilatory and hypotensive action of nitric oxide. The Na+,K+-ATPase activity in rat aorta depends on the balance between the level of reactive oxygen and nitrogen species (ROS and RNS), forma­tion of NO depots in the tissue of aorta as high- and low mo­lecular weight nitrosothiols, and also on the intensity of free-radical reactions resulting in the generation of hydroperoxide radicals. The results obtained suggest that NOS- and cGMP-dependent pathway takes part in Na+,K+-ATPase activation by LPS and NG, but the enzyme inhibition by nitric oxide in vivo is not cGMP-dependent and is determined by the activation of free-radical reactions and dramatic enhancement of nitrosylation level in rat aorta tissue.