Endothelin mediates renal vascular memory of a transient rise in perfusion pressure 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. Acutel-NMA increased blood pressure (BP, ∼20%) and renal vascular resistance (RVR) rose (∼50%) in the right kidneys that were always exposed to high RPP. In group 1, the left kidney was exposed to a transient increase (5 min) in RPP which was then normalized, and the rise in RVR was 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 kidney. In group 3, rats were pretreated with the endothelin (ET) receptor antagonist Bosentan, immediately before exposure of the left kidney to a transient increase in RPP, and the rise in RVR was also attenuated relative to the right kidney. NOS inhibition resulted in a natriuresis and diuresis in the right kidneys, and ∼50% of the natriuresis persisted in the left kidney of group 2, in the absence of any rise in RPP. ET antagonism completely prevented the natriuresis and diuresis in response to acutel-NMA in both left and right kidneys. These data suggest that transient exposure to high RPP by NOS inhibition prevents an appropriate vasodilatory response when RPP is lowered, due to the intrarenal action of ET.