BLOCKADE OF DISTAL NEPHRON SODIUM-TRANSPORT ATTENUATES PRESSURE NATRIURESIS IN DOGS

The sodium excretory responses (UNaV) to acute changes in renal arteri al pressure (RAP) during blockade of distal nephron sodium transport w ere evaluated in seven sodium-replete anesthetized dogs. The major dis tal sodium entry pathways were blocked by intrarenal infusion of amilo ride (AM, 10(-5) mol/L) and bendroflumethiazide (BZ, 10(-6) mol/L). In fusion of AM plus BZ caused slight increases in renal blood flow (RBF, 4.1+/-0.5 to 4.6+/-0.4 mL.min(-1).g(-1); P<.001) but no changes in gl omerular filtration rate (GFR, 0.96+/-0.05 to 1.01+/-0.07 mL.min(-1).g (-1); P=NS) or autoregulatory efficiency of RBF and GFR. There were si gnificant increases in UNaV (2.7+/-0.7 to 5.2+/-0.6 mu mol.min(-1).g(- 1)) and fractional excretion of sodium (FE(Na), 1.8+/-0.4% to 3.5+/-0. 3%) and decreases in potassium excretion (0.59+/-0.10 to 0.35+/-0.06 m u mol.min(-1).g(-1)) during AM plus BZ infusion. During the control pe riod and during repeat measurements in time control studies, decreases in RAP (150 to 100 mm Hg) elicited the usual decreases in UNaV (slope , 0.022+/-0.007 mu mol.min(-1).g(-1).mm Hg-1; P<.01). After administra tion of AM plus BZ, there was a marked attenuation of the pressure-nat riuretic responses, and the slopes of the RAP versus UNaV and RAP vers us FE(Na) relations at RAP levels above 100 mm Hg were not significant ly different from zero. However, the pressure-natriuresis response was maintained at arterial pressure between 75 and 100 mm Hg. Addition of the nitric oxide (NO) synthesis inhibitor, nitro-L-arginine (NLA, 50 mu g.kg(-1).min(-1)) during AM plus BZ infusion resulted in decreases in RBF to 3.79+/-0.34 mL.min(-1).g(-1), UNaV to 2.89+/-0.16 mu mol.min (-1).g(-1), and FE(Na) to 2.13+/-0.09% without appreciable changes in GFR. The pressure-natriuretic responses remained attenuated during NLA infusion. These data suggest that the sodium entry pathways in the di stal nephron are involved in mediating the arterial pressure-induced c hanges in sodium excretion occurring at RAPs above 100 mm Hg. The redu ced sodium excretion caused by NLA during distal nephron blockade sugg ests that NO influences additional sodium excretory mechanisms.