Sütö T, Losonczy G, Qiu C, Hill C, Samsell L, Ruby J, Charon N, Venuto R, Baylis C
Department of Physiology, West Virginia University, Robert C. Byrd Health Sciences Center, Morgantown, USA.
Kidney Int. 1995 Oct;48(4):1272-7. doi: 10.1038/ki.1995.411.
NO2 + NO3 (NOx), 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 (UNOXV) 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 UNOxV, 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 UNOX V is seen with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in UNOX V, and SNP lowers BP but not RVR and results in a reduced UNOX V. None of the diuretics employed should stimulate the NO system or lower RVR; however, the proximally acting agents, acetazolamide and D-arg increased UNOx V, while the loop diuretic furosemide had little effect. H2O diuresis (a distal event) led to a fall in UNOx V. These data suggest that NOx is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in UNOx V. Also, our results show that the relationship between UNOx V and UcGMP V is unpredictable. Therefore, we conclude that measurements of acute changes in UNOxV and/or UcGMP V should be interpreted cautiously, since they may reflect altered tubular handling of NOx rather than the acute activity of the systemic and/or renal NO systems.
NO2 + NO3（氮氧化物）是NO的稳定氧化产物，而环磷酸鸟苷（cGMP）被广泛认为是体内NO生成的指标。目前尚不清楚尿中亚硝酸盐+硝酸盐排泄量（UNOXV）的急性变化是否可用于反映肾脏和/或全身NO生成的急性变化。本研究在清醒大鼠中进行，以探究以下操作对UNOXV急性变化的影响：（a）增强NO生成；（b）发挥利尿剂作用。L-精氨酸（L-arg）和乙酰胆碱（Ach）可使肾血管阻力（RVR）同等程度地依赖NO降低，但L-arg使UNOXV升高幅度更大。D-精氨酸不刺激NO生成，无肾血管舒张作用，但可使UNOXV大幅升高，而硝普钠（SNP）降低血压但不降低RVR，并导致UNOXV降低。所使用的利尿剂均不应刺激NO系统或降低RVR；然而，近端作用药物乙酰唑胺和D-精氨酸使UNOxV升高，而袢利尿剂呋塞米作用甚微。水利尿（远端事件）导致UNOxV降低。这些数据表明，NOx在近端小管被广泛重吸收，抑制近端重吸收会导致UNOxV升高。此外，我们的结果表明UNOxV与尿中环磷酸鸟苷排泄量（UcGMP V）之间的关系不可预测。因此，我们得出结论，对UNOxV和/或UcGMP V急性变化的测量应谨慎解读，因为它们可能反映了肾小管对NOx处理的改变，而非全身和/或肾脏NO系统的急性活性。
