Mediation of vascular relaxation in epineurial arterioles of the sciatic nerve: effect of diabetes in type 1 and type 2 diabetic rat models.
Previously, the authors have reported that acetylcholine-induced vascular relaxation in epineurial arterioles of the sciatic nerve is mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Furthermore, they have demonstrated that acetylcholine-induced vasodilation in these vessels is impaired in streptozotocin-induced (type 1) and ZDF obese (type 2) diabetic rats. In the present study, the authors sought to determine the effect of diabetes on NO- and EDHF-mediated vasodilation in epineurial arterioles. In epineurial arterioles from nondiabetic Sprague-Dawley rats, NO and EDHF are equivalent in regard to their contribution to acetylcholine-induced vascular relaxation. In contrast, NO accounts for a greater portion of acetylcholine-induced vascular relaxation in normal glycemic ZDF lean rats. Following 4 weeks of hyperglycemia, the EDHF component of acetylcholine-induced vascular relaxation was totally inhibited in both streptozotocin-induced and ZDF obese diabetic rats. Vasodilation mediated by NO was still active in epineurial arterioles from both type 1 and type 2 diabetic rat models. These data suggest that diabetes causes an impairment in EDHF-mediated vascular relaxation and that interventions directed at improving EDHF production or bioactivity may improve vascular function in epineurial arterioles in diabetes.
Coppey
Lawrence J
LJ
Veteran Affairs Medical Center, Diabetes Endocrinology Research Center, and Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA.
Gellett
Jill S
JS
Yorek
Mark A
MA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D001685:Biological Factors / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D012584:Sciatic Nerve / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D007213:Indomethacin