The Influence of Nanomolar Ouabain on Vascular Pressor Responses is Modulated by the Endothelium

Ouabain has been shown to be an endogenous hormone that is synthesized and released from the adrenal cortex and is present in nanomolar to subnanomolar concentrations in plasma. It has been proposed that endogenous ouabain can increase vascular resistance and induce hypertension. This substance inhibits the Na-pump activity, which leads to intracellular Na accumulation and ultimately to increased vascular tone. It is also suggested that circulating ouabain influences the vascular smooth muscle response to vasopressor substances. However, the mechanisms by which low concentrations of ouabain influence the smooth muscle, directly or acting through the endothelium, have not been completely elucidated. We tested the hypothesis that the endothelium exerts a modulatory effect on the actions of ouabain. In these studies, isolated rat-tail vascular bed preparations obtained from normotensive animals were used. The effects of 10 nM ouabain on the reactivity of the vascular smooth muscle to phenylephrine were determined under conditions in which endothelial function was preserved or reduced by endothelial removal and treatment with N-nitro-L-arginine methyl ester (L-NAME) or potassium channel blocker (tetraethylammonium; TEA). Results showed that ouabain enhanced the reactivity to phenylephrine. The enhancement of the reactivity to phenylephrine produced by ouabain was potentiated by deendothelialization and by using TEA, but it was reduced by treatment with L-NAME. The effect of 10 nM ouabain on the functional activity of the Na,K-adenosine triphosphatase (ATPase) also was evaluated. Na,K-ATPase activity was reduced after 1-h treatment with ouabain. These results suggested that low concentrations of ouabain reduced the functional activity of the Na,K-ATPase and stimulated the release of a potassium channel opener, suggesting that the effects of ouabain are partially modulated by the endothelium.