| Autor: |
Pieper, Galen M., Dondlinger, Lynn A. |
| Zdroj: |
The Journal of Pharmacology and Experimental Therapeutics; November 1997, Vol. 283 Issue: 2 p684-691, 8p |
| Abstrakt: |
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 vitroon 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 vitrowith 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 byl-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 vitroby provision of substrate for nitric oxide synthase. |
| Databáze: |
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