Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilation of normal rat arterioles.
Arteriolar dilation to endothelium-derived relaxing factor (EDRF) is suppressed early in diabetes mellitus. The purpose of this study was to determine whether acute exposure to a hyperglycemic media can suppress EDRF function of normal arterioles. Dilation of intestinal arterioles to iontophoretically applied acetylcholine (ACh) and nitroprusside was measured in normoglycemic rats before and after 1 h of topical exposure to isotonic solutions containing D-glucose concentrations of 200, 300, and 500 mg/100 ml. Exposure to a D-glucose concentration of 200 mg/100 ml had no effect on vasodilation to ACh. D-Glucose concentrations of both 300 and 500 mg/100 ml caused significant suppression of the responses: for example, at the approximate 50% effective dosage (100 nA), the dilatory response was decreased by 60% at a D-glucose concentration of 300 mg/100 ml and 55% at a D-glucose concentration of 500 mg/100 ml. Responses to nitroprusside were not significantly (P < 0.05) impaired after exposure to D-glucose concentrations of 200, 300, or 500 mg/100 ml. Exposure to an isotonic L-glucose concentration of 500 mg/100 ml for 1 h had no significant (P > 0.05) effect on responses to ACh. Pretreatment with superoxide dismutase, catalase, indomethacin, or meclofenamic acid preserved EDRF-mediated vasodilation during exposure to a D-glucose concentration of 500 mg/100 ml at almost all the ACh dosages tested. These results indicate that oxygen radicals formed in part by increased eicosanoid synthesis during exposure to D-glucose hyperglycemia interfere with the EDRF mechanism before its action on the microvascular smooth muscle.
Bohlen
H G
HG
Department of Physiology and Biophysics, Indiana University Medical School, Indianapolis 46122.
Lash
J M
JM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012016:Reference Values; D014664:Vasodilation / Q000502:physiology*
D017382:Reactive Oxygen Species; D009599:Nitroprusside; D009569:Nitric Oxide; D005947:Glucose; D000109:Acetylcholine