Biological Evaluation of the Nitric Oxide-Trapping Agent, N-Methyl-D-glucamine Dithiocarbamate-Fe2+, as a Probe of Nitric Oxide Activity Released From Control and Diabetic Rat Endothelium.

• Pieper Galen M.

  Department of Transplant Surgery, Medical College of Wisconsin, Froedtert Memorial Hospital

• Lai Ching-San

  Medinox, Inc.

Bibliographic Information

Other Title

• Biological Evaluation of the Nitric Oxide-Trapping Agent,N-Methyl-D-Glucamine Dithiocarbamate-Fe〔2+〕,as a Probe of Nitric Oxide Activity Released From Control and Diabetic Rat Endothelium

Abstract

We utilized the nitric oxide (NO) scavenger N-methyl-D-glucamine dithiocarbamate-Fe²⁺ (MGD-Fe) to characterize the role of NO in basal and acetylcholine (ACh)-stimulated relaxation arising from the endothelium of control vs diabetic rat aortic rings. In phenylephrine-contracted rings, MGD-Fe produced an additional increment in tension that was indomethacin-insensitive (i.e., excluding a role of prostanoids in this action). This MGD-Fe-sensitive component was more pronounced in control rings than diabetic rings and of the same magnitude achieved in rings without MGD-Fe treatment after removal of endothelium or treatment with the NO synthase inhibitor L-nitroarginine (L-NA). This suggests complete scavenging of basal NO by MGD-Fe and supports reduced basal NO in diabetic rings. ACh fully relaxed both control and diabetic rings. This relaxation was abolished by removal of the endothelium and was inhibited by L-NA (by 100% and 90% in control and diabetic rings, respectively). In contrast, MGD-Fe only partially inhibited ACh-induced relaxation in control (65±5% inhibition) and diabetic (41±11% inhibition) rings. The MGD-Fe-resistant component was not further modified by indomethacin. Addition of L-arginine (L-ARG) (but not D-arginine (D-ARG) enhanced the ACh-induced relaxation of MGD-Fe-treated diabetic (but not control) rings. These data provide evidence about endothelium-dependent relaxation in control and diabetic rings which cannot be discerned by use of L-NA alone. This study suggests that ACh produces a NO synthase-dependent vasodilation, a portion of which is due to free NO radical (·NO) or due to NO in a form or location that is unavailable for scavenging by MGD-Fe.

Journal

• The Japanese Journal of Pharmacology

  The Japanese Journal of Pharmacology 80 (4), 359-370, 1999

  The Japanese Pharmacological Society

Keywords

• Nitric oxide
• Endothelium
• Dithiocarbamate
• Arginine
• Diabetes mellitus

Details

• CRID: 1390001204284878080
• NII Article ID: 10008195871
• NII Book ID: AA00691188
• DOI: 10.1254/jjp.80.359
• COI: 1:CAS:528:DyaK1MXlslWlt7k%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL BIB ID: 4837035
• PubMed: 10496337
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4837035
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819308327?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819308327?httpAccept=text/plain
• Web Site: https://www.jstage.jst.go.jp/article/jjp/80/4/80_4_359/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2000032898
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed