SUPEROXIDE-DISMUTASE RESTORES THE INFLUENCE OF NITRIC-OXIDE ON RENAL ARTERIOLES IN DIABETES-MELLITUS

Experiments were performed to determine the influence of endogenous ni tric oxide (NO) on basal arteriolar diameter in kidneys from diabetic rats and to evaluate the role of superoxide anions as modulators of NO activity under these conditions. Male Sprague-Dawley rats were inject ed with streptozotocin (STZ, 65 mg/kg iv) and received insulin via ip osmotic minipumps (3 U/kg per day). Sham rats received vehicle treatme nts. Videomicroscopy was used, in conjunction with the in vitro blood- perfused juxtamedullary nephron technique, to visualize renal afferent and efferent arterioles 2 wk after the onset of diabetes. Baseline af ferent arteriolar inside diameter was greater in STZ (32 +/- 2 mu m) t han in sham rats (24 +/- 2 mu m). Efferent arteriolar diameter did not differ between STZ (24 +/- 2 mu m) and sham rats(21 +/- 1 mu m). In k idneys from sham rats, N-omega-nitro-L-arginine (L-NNA, an NO synthase inhibitor) decreased arteriolar diameters in a concentration-dependen t manner, with 100 mu M L-NNA significantly reducing both afferent (13 +/- 2%) and efferent (11 +/- 1%) diameters. In kidneys from STZ rats, 100 mu M L-NNA reduced afferent and efferent diameters by only 3 +/- 1 and 4 +/- 1%, respectively, indicating a suppressed arteriolar influ ence of NO. In STZ kidneys treated with superoxide dismutase (SOD, 150 U/mL), afferent and efferent arteriolar L-NNA responses were restored to levels comparable to those of SOD-treated and untreated sham kidne ys. These observations suggest that suppressed SOD activity reduces th e tonic influence of NO on renal arterioles during the early stage of diabetes mellitus, perhaps through allowing the accumulation of NO-sca venging superoxide anions.