ACUTE CHANGES IN URINARY-EXCRETION OF NITRITE PLUS NITRATE DO NOT NECESSARILY PREDICT RENAL VASCULAR NO PRODUCTION

NO2 + NO3 (NOx) the stable oxidation products of NO, and cGMP are wide ly accepted as indices of in vivo NO production. Whether acute changes in urinary excretion of nitrite + nitrate (UNOXV) can be taken to ref lect acute changes in renal and/or systemic NO production is not known . The present studies were conducted in the conscious rat to investiga te the effect on acute changes in UNOXV, of maneuvers that (a) enhance NO production and (b) act as diuretics. L-arginine (L-arg) and acetyl choline (Ach) produce equivalent NO dependent falls in renal vascular resistance (RVR), but a much greater increase in UNOXV is seen with L- arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in UNOXV, and SNP lowers BP but not RVR and results in a reduced UNOXV. None of the diuretics employed should sti mulate the NO system or lower RVR; however, the proximally acting agen ts, acetazolamide and D-arg increased UNOXV, while the loop diuretic f urosemide had little effect. H2O diuresis (a distal event) led to a fa ll in UNOXV. These data suggest that NOx is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in UNOXV. Also, our results show that the relationship between UNOXV and UcGMPV is unpredictable. Therefore, we conclude tha t measurements of acute changes in UNOXV and/or UcGMPV should be inter preted cautiously, since they may reflect altered tubular handling of NOx rather than the acute activity of the systemic and/or renal NO sys tems.