Intrarenal nitric oxide activity and pressure natriuresis in anesthetized dogs.

Recent studies have indicated that changes in intrarenal nitric oxide (NO) production participate in mediating arterial pressure-induced changes in urinary sodium excretion. Until recently, however, the means to measure changes in intrarenal NO activity in vivo have not been available. For the present study, changes in renal tissue NO activities were assessed directly using an NO-selective microelectrode inserted into the cortical tissue of anesthetized dogs. Control studies demonstrated that the electrode was responsive to intrarenal bolus injections of acetylcholine and to the NO donor S-nitroso-acetylpenicillamine (SNAP). Intrarenal nitro-L-arginine (50 microg x kg(-1) x min(-1)) decreased renal tissue NO concentration by 593+/-127 nmol/L (P<0.05; n=7). Infusions of SNAP (1, 2, and 3 microg x kg(-1) x min(-1) for 25 minutes) in nitro-L-arginine-treated dogs (n=5) resulted in dose-dependent increases in renal tissue NO activity, which showed a positive correlation with changes in urinary excretion rates of NO metabolites, nitrates and nitrites, (r=0.62, P<0.05) and sodium (r=0.78, P<0.01). During graded reductions of renal arterial pressure within the autoregulatory range (144+/-3 to 73+/-2 mm Hg; n=10), there were decreases in tissue NO activity that were positively correlated with changes in renal arterial pressure (r=0.45; P<0.05), urinary nitrate/nitrite excretion (r=0.64, P<0.005), and urinary sodium excretion (r=0.46; P<0.05). These data support the hypothesis that acute changes in renal arterial pressure result in alterations in intrarenal NO activity, which may be responsible for the associated changes in sodium excretion.