RENAL EFFECTS OF ACUTE AMINO-ACID INFUSION IN HYPERTENSION INDUCED BYCHRONIC NITRIC-OXIDE BLOCKADE

L-Arginine is the physiological substrate of nitric oxide, a vasodilat or that controls blood pressure and renal hemodynamics in the basal st ate. In the present studies, we produced chronic nitric oxide blockade by oral administration of the L-arginine analogue N-G-ni tro-L-argini ne methyl ester, which produced sustained hypertension and increased r enal vascular resistance in conscious rats. Acute excess L-arginine ha d little effect on blood pressure but completely normalized renal vasc ular resistance and increased renal plasma flow in chronically nitric oxide-blocked hypertensive rats. In contrast to L-arginine, D-arginine had no renal hemodynamic effects in either normal or chronically nitr ic oxide-blocked rats. Acutely administered glycine was ineffective in vasodilating the chronically nitric oxide-blocked rat kidney, in a do se that produced renal vasodilation in normal rats. These findings ind icate the following: (1) Hypertension induced by chronic nitric oxide blockade due to substituted L-arginine analogue cannot be acutely reve rsed with excess L-arginine, suggesting that the maintenance of the hy pertension is not solely caused by competitive inhibition of nitric ox ide production; (2) in contrast, the kidney remains responsive to L-ar ginine whereas the renal vasodilator response to glycine is abolished in this model of hypertension.