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

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We utilized the nitric oxide (NO) scavenger <I>N</I>-methyl-D-glucamine dithiocarbamate-Fe<SUP>2+</SUP> (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.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 80(4), 359-370, 1999-08-01

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008195871
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4837035
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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