Plasma and vascular tissue arginine are decreased in diabetes: acute arginine supplementation restores endothelium-dependent relaxation by augmenting cGMP production.
Arginine is a precursor amino acid for the synthesis of nitric oxide by nitric oxide synthase. A defect in arginine supply could regulate nitric oxide-mediated, endothelium-dependent relaxation. In this study, we evaluated the effect of supplementation with L-arginine given in vitro on both functional relaxation and cGMP generation in response to acetylcholine in the streptozotocin-induced diabetic rat aorta. The concentration of arginine in plasma and aortic tissue were both decreased by diabetes. Acute incubation in vitro with L-arginine augmented the impaired relaxation to acetylcholine in diabetic rings although not altering relaxation in control rings. L-Arginine also enhanced relaxation to acetylcholine in diabetic rings incubated in the presence of either indomethacin or tetraethylammonium to inhibit cyclooxygenase activity and potassium channel activity, respectively. Acetylcholine-stimulated cGMP generation (which was blocked by L-nitroarginine) was diminished in diabetic rings compared with control rings. L-Arginine restored cGMP in diabetic rings (with but not without endothelium) to levels similar to control rings. L-Arginine did not alter cGMP generated by nitroglycerin. Incubation with L-arginine had no effect on acetylcholine-stimulated cGMP generation in control rings (with and without endothelium). These data suggest a potential intracellular substrate deficiency in nitric oxide production by diabetic endothelium which can be overcome acutely in vitro by provision of substrate for nitric oxide synthase.
Pieper
G M
GM
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee Wisconsin 53226, USA.
Dondlinger
L A
LA
D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D001835:Body Weight; D006152:Cyclic GMP / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D014664:Vasodilation
D009569:Nitric Oxide; D013311:Streptozocin; D001120:Arginine; D006152:Cyclic GMP