Angiotensin II and Prostaglandin Interactions on Systemic andRenal Effects of L-NAME in Humans

For investigation of whether interactions between prostaglandins and angiotensin II modulate renal response to acute nitric oxide synthesis inhibition in humans, seven young volunteers who were kept on a 240-mM Na diet underwent four experiments with 90 min of infusion of 3.0 mg/kg.min21 NG-nitro-L-arginine methyl ester (L-NAME), each preceded by a 3-d treatment with placebo (PL), 50 mg of losartan (LOS), 75 to 125 mg of indomethacin (IND), or both drugs. Mean arterial pressure (MAP), GFR, effective renal plasma flow (ERPF), and Na excretion rate (UNaV) were measured at baseline and from 0 to 45 min and 45 to 90 min of L-NAME infusion. After PL, L-NAME reduced GFR by 5% at 45 min (P , 0.05) and by 9% at 90 min (P , 0.001), ERPF by 11 to 17% (P , 0.001), and UNaV by 28 to 45% (P , 0.001). MAP, unchanged at 45min, rose by 5% (P , 0.001) at 90 min. LOS prevented pressor but not renal effects of L-NAME. With L-NAME1IND, MAP rose even at 45 min (15%; P , 0.001 versus baseline) with a 10% rise at 90 min (P , 0.001). Changes in GFR (213 to 220%), ERPF (219 to226%), and UNaV (251 to270%) were greater than those with L-NAME1PL or L-NAME1LOS (P , 0.05 to 0.001). With L-NAME1IND1LOS, MAP did not increase, and GFR, ERPF, and UNaV fell much less than with L-NAME1IND alone (P , 0.02 to 0.001) with no differences versus PL or LOS alone. Angiotensin II blockade does not affect renal changes caused by L-NAME but prevents their potentiation by prostaglandin inhibition. Thus, endogenous prostaglandins counteract renal actions of endogenous angiotensin II in Na repleted humans even when nitric oxide synthesis is inhibited