Endothelial dysfunction in mesenteric resistance arteries of diabetic rats: role of free radicals.
Diabetes was induced in rats by an injection of streptozotocin (55 mg/kg). Endothelium-dependent relaxations in mesenteric resistance arteries (luminal diameter 210 +/- 20 microns) of control and diabetic rats were compared in myographs. Acetylcholine induced endothelium-dependent relaxations that were mediated by nitric oxide (EDNO). EDNO-mediated relaxations were impaired in diabetic arteries; concentrations of acetylcholine required to produce 50% relaxation (ED50) of activated arteries were 5 nM in control and 13.5 nM in arteries from diabetic rats studied after 6 wk (P < 0.05). The impairment in relaxation worsened with duration of the diabetes; ED50 for acetylcholine increased to 63 and 100 nM in diabetic arteries studied after 16 and 24 wk of diabetes, respectively. NG-nitro-L-arginine produced 5.5- and 16-fold decreases in sensitivity of control and diabetic arteries to acetylcholine. NG-nitro-L-arginine produced at least as much inhibition of acetylcholine relaxations in diabetic arteries, indicating that the impaired relaxation noted in diabetic arteries does not result from decreased production of EDNO. EDNO-mediated relaxations in diabetic arteries were impaired by increased production of endothelium-derived free radicals. Superoxide dismutase, a scavenger of superoxide anion, and dimethylthiourea, a scavenger of hydroxyl radicals, normalized EDNO-mediated relaxations in diabetic arteries. The ED50 values for acetylcholine were 13.5, 5.5, and 4 nM for untreated and SOD- and DMTU-treated diabetic arteries, respectively (P < 0.05 for treated vs. untreated arteries). Superoxide anion and hydroxyl radicals appear to block EDNO-mediated relaxation by inactivating EDNO.(ABSTRACT TRUNCATED AT 250 WORDS)
Diederich
D
D
Department of Medicine, University of Kansas Medical Center, Kansas City 66103.
Skopec
J
J
Diederich
A
A
Dai
F X
FX
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005609:Free Radicals; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D051381:Rats; D011921:Rats, Inbred WKY; D012016:Reference Values; D014655:Vascular Resistance; D014664:Vasodilation
D005609:Free Radicals; D009569:Nitric Oxide