Abstract
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 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 vitro by provision of substrate for nitric oxide synthase.
Footnotes
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Send reprint requests to: Dr. Galen M. Pieper, Dept. of Transplant Surgery, Medical College of Wisconsin, Froedtert Memorial Hospital, 9200 West Wisconsin Avenue, Milwaukee WI 53226.
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↵1 This work was supported by grant HL47072 from the National Institutes of Health, Heart and Lung Institute.
- Abbreviations:
- NO
- nitric oxide
- NE
- norepinephrine
- l-NA
- l-nitroarginine
- l-ARG
- l-arginine
- d-ARG
- d-arginine
- ACH
- acetylcholine
- TEA
- tetraethylammonium
- NTG
- nitroglycerin
- Received May 2, 1997.
- Accepted July 23, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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