Augmentation of diabetes-associated renal hyperfiltration and nitric oxideproduction by pregnancy in rats

We tested the hypothesis that pregnancy might increase diabetes-associated nitric oxide (NO) production and renal hyperfiltration. Two weeks following i.v. streptozotocin (40 mg/kg), mean arterial pressure (MAP) was not modif ied by diabetes; glomerular filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF) were higher in pregnant than in virgin control s and increased by diabetes to a greater extent in pregnant than in virgin rats. Urinary volume (UV), creatinine, albumin and sodium (UNAV) were signi ficantly increased by diabetes. Diabetes led to an increase in renal, cardi ac, aortic and uterine but not in placental NO synthase activities. Infusio n of N-G-nitro-L-arginine (L-NA) caused a dose-dependent reduction in GFR, RPF, plasma NO2-/NO3-, UV and UNAV; in general, diabetes increased these ef fects to a greater extent in pregnant than in virgin rats. L-NA increased M AP in all groups of rats but did not alter FF. Diabetes did not alter respo nses of thoracic aorta rings to vasoconstrictor effects of phenylephrine an d the vasorelaxant effects of sodium nitroprusside but increased endotheliu m-dependent relaxant effects of acetylcholine. In general the effects of di abetes of 7 days duration were similar to those described above for diabete s of 14 days duration. These data suggest that diabetes-associated renal hy perfiltration and NO production are augmented by pregnancy.