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Journal of Pharmacology and Experimental Therapeutics

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OtherAUTONOMIC PHARMACOLOGY

Plasma and Vascular Tissue Arginine Are Decreased in Diabetes: Acute Arginine Supplementation Restores Endothelium-Dependent Relaxation by Augmenting cGMP Production

Galen M. Pieper and Lynn A. Dondlinger
Journal of Pharmacology and Experimental Therapeutics November 1997, 283 (2) 684-691;
Galen M. Pieper
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Lynn A. Dondlinger
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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

  • 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.

  • ↵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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Journal of Pharmacology and Experimental Therapeutics
Vol. 283, Issue 2
1 Nov 1997
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OtherAUTONOMIC PHARMACOLOGY

Plasma and Vascular Tissue Arginine Are Decreased in Diabetes: Acute Arginine Supplementation Restores Endothelium-Dependent Relaxation by Augmenting cGMP Production

Galen M. Pieper and Lynn A. Dondlinger
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 684-691;

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OtherAUTONOMIC PHARMACOLOGY

Plasma and Vascular Tissue Arginine Are Decreased in Diabetes: Acute Arginine Supplementation Restores Endothelium-Dependent Relaxation by Augmenting cGMP Production

Galen M. Pieper and Lynn A. Dondlinger
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 684-691;
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