Responses to Acute Changes in Arterial Pressure on Renal Medullary Nitric Oxide Activity in Dogs

A direct relationship between renal arterial pressure (RAP) and cortical tissue nitric oxide (NO) activity in the canine kidney was reported earlier. We have conducted further experiments to evaluate medullary NO responses to alterations in RAP with the use of a NO-selective microelectrode inserted into the renal medulla of 6 anesthetized, sodium-replete dogs. Graded reductions in RAP (from 140 to 80 mm Hg) elicited decreases in medullary tissue NO concentration, with a slope of 10.2±4.5 nmol · L · mm Hg. These changes in NO levels were associated with decreases in urinary excretion rate of nitrate and nitrite (UNOxV; control value, 1.7±0.03 nmol · min · g; slope, 0.02±0.004 nmol · min · g · mm Hg) and sodium excretion (UNa V; control, 3.2±0.7 μmol · min · g; slope, 0.06±0.02 μmol · min · g · mm Hg) without changes in glomerular filtration rate control (0.84±0.06 mL · min · g). Intra-arterial administration of the NO synthase inhibitor N-nitro-L-arginine (NLA; 50 μg · kg · min) decreased medullary NO concentration by 218±55 nmol · L (n=5) and attenuated the relationship between RAP and NO concentration (slope, 2.7±2.2 nmol · L · mm Hg). NLA infusion decreased UNOx V (0.8±0.06 nmol · min · g) and UNa V (1.1±0.2 μmol · min · g) without changes in glomerular filtration rate and attenuated RAP versus UNox V and UNa V relationships. Total and regional blood flows, as measured by electromagnetic and laser Doppler needle flow probes, respectively, remained autoregulated both before and during NLA infusion. These data support the hypothesis that acute changes in RAP elicit changes in intrarenal NO production, which may participate in the mediation of pressure natriuresis.