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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概要
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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.
- 社団法人 日本薬理学会の論文
- 1999-08-01
著者
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Pieper Galen
Department Of Transplant Surgery Medical College Of Wisconsin Froedtert Memorial Hospital
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LAI Ching-San
Medinox Inc.