Bank N, Aynedjian H S
Department of Medicine, Montefiore Medical Center, Bronx, New York.
Kidney Int. 1993 Jun;43(6):1306-12. doi: 10.1038/ki.1993.183.
In order to study the role of EDRF in diabetic hyperfiltration, the concentrations of NO2-/NO3-, the stable products of nitric oxide (NO), were measured in arterial plasma, urine, and renal venous blood in streptozotocin diabetic rats and normal control rats. In additional experiments, the renal hemodynamic and blood pressure responses to graded doses of an inhibitor of NO synthesis (Nitro-L-arginine; NLA) were measured. We found that plasma and urinary levels of NO2/NO3 are significantly higher in STZ diabetic rats (10 to 15 days) than in normal rats. Renal blood flow and GFR fell comparably in diabetic and normal rats in response to NLA infusion, although the absolute levels of RBF and GFR remained significantly higher in the diabetic rats at all doses of the inhibitor. Mean arterial blood pressure (MAP) rose in response to NLA administration, but the increase in the diabetic rats was significantly blunted as compared with the normal rats. Similarly, renal vascular resistance (RVR) increased less in the diabetic than in the normal rats at comparable doses of NLA. The blunted vasoconstrictor responses to NLA were accompanied by a smaller reduction in the levels of NO2-/NO3- in the urine of the diabetic versus the normal rats. These findings suggest that NO synthesis is increased in diabetic rats manifesting hyperfiltration and are consistent with the view that excess NO synthesis contributes to renal hyperfiltration.
为了研究内皮舒张因子（EDRF）在糖尿病性超滤中的作用，我们测定了链脲佐菌素诱导的糖尿病大鼠和正常对照大鼠动脉血浆、尿液及肾静脉血中一氧化氮（NO）的稳定产物亚硝酸盐/硝酸盐（NO2-/NO3-）的浓度。在另外的实验中，我们测定了给予不同剂量的NO合成抑制剂（硝基-L-精氨酸；NLA）后肾脏血流动力学和血压的反应。我们发现，链脲佐菌素诱导的糖尿病大鼠（10至15天）血浆和尿液中的NO2/NO3水平显著高于正常大鼠。给予NLA后，糖尿病大鼠和正常大鼠的肾血流量和肾小球滤过率均相应下降，尽管在所有剂量的抑制剂作用下，糖尿病大鼠的肾血流量和肾小球滤过率的绝对值仍显著高于正常大鼠。给予NLA后平均动脉血压（MAP）升高，但与正常大鼠相比，糖尿病大鼠的升高幅度明显减弱。同样，在给予相同剂量NLA时，糖尿病大鼠肾血管阻力（RVR）的增加幅度小于正常大鼠。糖尿病大鼠对NLA的血管收缩反应减弱，同时其尿液中NO2-/NO3-水平的降低幅度也小于正常大鼠。这些发现表明，表现为超滤的糖尿病大鼠体内NO合成增加，这与过量NO合成导致肾脏超滤的观点一致。
