Acute changes in urinary excretion of nitrite + nitrate do not necessarily predict renal vascular NO production

Acute changes in urinary excretion of nitrite + nitrate do not necessarily predict renal vascular NO production. NO 2 + NO 3 (NO x ), the stable oxidation products of NO, and cGMP are widely accepted as indices of in vivo NO production. Whether acute changes in urinary excretion of nitrite + nitrate (U NOX V) can be taken to reflect acute changes in renal and/or systemic NO production is not known. The present studies were conducted in the conscious rat to investigate the effect on acute changes in U NOx V, of maneuvers that (a) enhance NO production and (b) act as diuretics. L-arginine (L-arg) and acetylcholine (Ach) produce equivalent NO dependent falls in renal vascular resistance (RVR), but a much greater increase in U NOX V is seen with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in U NOX V, and SNP lowers BP but not RVR and results in a reduced U NOX V. None of the diuretics employed should stimulate the NO system or lower RVR; however, the proximally acting agents, acetazolamide and D-arg increased U NOx V, while the loop diuretic furosemide had little effect. H 2 O diuresis (a distal event) led to a fall in U NOx V. These data suggest that NO x is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in U NOx V. Also, our results show that the relationship between U NOx V and U cGMP V is unpredictable. Therefore, we conclude that measurements of acute changes in U NOx V and/or U cGMP V should be interpreted cautiously, since they may reflect altered tubular handling of NO x rather than the acute activity of the systemic and/or renal NO systems.