Superoxide dismutase restores the influence of nitric oxide on renal arterioles in diabetes mellitus.
Experiments were performed to determine the influence of endogenous nitric 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 injected with streptozotocin (STZ, 65 mg/kg i.v.) and received insulin via ip osmotic minipumps (3 U/kg per day). Sham rats received vehicle treatments. 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 afferent arteriolar inside diameter was greater in STZ (32 +/- 2 microns) than in sham rats (24 +/- 2 microns). Efferent arteriolar diameter did not differ between STZ (24 +/- 2 microns) and sham rats (21 +/- 1 microns). In kidneys from sham rats, N omega-nitro-L-arginine (L-NNA, an NO synthase inhibitor) decreased arteriolar diameters in a concentration-dependent manner, with 100 microM L-NNA significantly reducing both afferent (13 +/- 2%) and efferent (11 +/- 1%) diameters. In kidneys from STZ rats, 100 microM L-NNA reduced afferent and efferent diameters by only 3 +/- 1 and 4 +/- 1%, respectively, indicating a suppressed arteriolar influence 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 kidneys. These observations suggest that suppressed SOD activity reduces the tonic influence of NO on renal arterioles during the early stage of diabetes mellitus, perhaps through allowing the accumulation of NO-scavenging superoxide anions.
Ohishi
K
K
Department of Physiology, Tulane University School of Medicine, New Orleans, LA, USA.
Carmines
P K
PK
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D051381:Rats; D012079:Renal Circulation / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase