Tempol blunts afferent arteriolar remodeling in chronic nitric oxide-deficient hypertension without normalizing blood pressure

Abstract

Renal preglomerular vessels play a central role in modulating renal function and injury, especially during conditions of renal hemodynamic stress such as hypertension. We evaluated whether improving the balance between nitric oxide (NO) and oxidative stress improves the morphological alterations of renal afferent arterioles that occur in NO deficiencyinduced hypertension. We measured indices of NO and oxidative stress and evaluated renal morphology and afferent arteriolar remodeling in rats treated with vehicle, L-NAME or L-NAME plus tempol (a superoxide dismutase mimetic) for 6 weeks. L-NAME-treated rats had hypertension, lower urinary and renal NO indices, higher renal cortical levels of TBARS, GSSG and GSSG/GSH. This was associated with significant eutrophic inward remodeling of the afferent arterioles; they had a marked decrease in arteriolar lumen area and a striking increase in arteriolar wall thickness and media to lumen ratio. Tempol did not significantly reduce blood pressure, but increased NO levels, decreased oxidative stress and partially blunted L-NAME-induced remodeling of afferent arterioles. L-NAME-induced remodeling of afferent arterioles is blunted by tempol. This beneficial effect on remodeling is associated with increases in NO indices, decreases in oxidative stress, without significant decreases in blood pressure. Thus, the balance between these components may contribute to the altered renal hemodynamics and function in this model.