Endothelin mediates renal vascular memory of a transient rise in perfusionpressure due to NOS inhibition

We investigated the renal responses to NO synthase (NOS) inhibition with N- monomethyl-L-arginine (L-NMA; 30 mg/kg) in anesthetized rats in which renal perfusion pressure (RPP) to the left kidney was mechanically adjusted. Acu te L-NMA increased blood pressure (BP, similar to 20%) and renal vascular r esistance (RVR) rose (similar to 50%) in the Fight kidneys that were always exposed to high RPP. In group 1, the left kidney was exposed to a transien t increase (5 min) in RPP which was then normalized, and the rise in RVR wa s similar to the right kidney. In group 2 the left kidney was never exposed to high RPP, and the rise in RVR was attenuated relative to the right kidn ey. In group 3, rats were pretreated with the endothelin (ET) receptor anta gonist Bosentan, immediately before exposure of the left, kidney to a trans ient increase in RPP, and the rise in RVR was also attenuated relative to t he right kidney. NOS inhibition resulted in a natriuresis and diuresis in t he right kidneys, and similar to 50% of the natriuresis persisted in the le ft kidney of group 2, in the absence of any rise in RPP. ET antagonism comp letely prevented the natriuresis and diuresis in response to acute L-NMA in both left and right kidneys. These data suggest that transient exposure to high RPP by NOS inhibition prevents an appropriate vasodilatory response w hen RPP is lowered, due to the intrarenal action of ET.