ROLE OF RENAL INTERSTITIAL HYDROSTATIC-PRESSURE IN NATRIURESIS OF SYSTEMIC NITRIC-OXIDE INHIBITION

Systemic inhibition of nitric oxide synthesis with N(G)-monomethyl-L-arginine (L-NMMA) increases renal perfusion pressure (RPP) and urinary sodium excretion. Increased RPP has been proposed as one of the mechanisms for the natriuresis caused by intravenous infusion Of L-NMMA. We tested the hypothesis that increases in renal interstitial hydrostatic pressure (RIHP) are required for the natriuresis of L-NMMA infusion. Experiments were performed in four groups of Sprague-Dawley rats in which partial aortic clamping and/or bilateral renal decapsulation was performed to control RPP and RIHP. Infusion of L-NMMA (15 mg/kg bolus + 500 mug . kg-1 . min-1 continuous infusion) increased RPP (DELTA+14 +/- 1 mmHg), RIHP (DELTA+3.6 +/- 0.7 mmHg), and fractional excretion of sodiUM (FE(Na); DELTA+2.4 +/- 0.6%, P < 0.005). When RPP was prevented from increasing by controlling RPP with an adjustable clamp around the suprarenal aorta, RIHP and FE(Na) did not significantly change. When only RIHP was held constant by bilateral renal decapsulation, FE(Na) was not significantly increased (DELTA+0.68 +/-0.36%, not significant), despite a significant rise in RPP (DELTA+18 +/- 2 mmHg, P < 0.001). Control of both RPP and RIHP prevented the increase in FE(Na). Thus, when renal interstitial pressure was controlled, the infusion of L-NMMA did not result in an increase in FE(Na). These results demonstrate that an increase in RIHP is a necessary component in the natriuresis due to systemic infusion of L-NMMA.