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

The sodium excretory responses (UNaV) to acute changes in renal arterial pressure (RAP) during blockade of distal nephron sodium transport were evaluated in seven sodium-replete anesthetized dogs. The major distal sodium entry pathways were blocked by intrarenal infusion of amiloride (AM, 10(-5) mol/L) and bendroflumethiazide (BZ, 10(-6) mol/L). Infusion 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 glomerular 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 significant 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 mu mol.min(-1).g(-1)) during AM plus BZ infusion. During the control period 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 administration of AM plus BZ, there was a marked attenuation of the pressure-natriuretic responses, and the slopes of the RAP versus UNaV and RAP versus FE(Na) relations at RAP levels above 100 mm Hg were not significantly 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 distal nephron are involved in mediating the arterial pressure-induced changes in sodium excretion occurring at RAPs above 100 mm Hg. The reduced sodium excretion caused by NLA during distal nephron blockade suggests that NO influences additional sodium excretory mechanisms.