Nicorandil metabolism in rat myocardial mitochondria

被引:20
作者
Sakai, K [1 ]
Akima, M [1 ]
Saito, K [1 ]
Saitoh, M [1 ]
Matsubara, S [1 ]
机构
[1] Chugai Pharmaceut Co Ltd, Cent Res Labs, Toshima Ku, Tokyo 1718545, Japan
关键词
nicorandil and rats; myocardial mitochondria; denitration; nitric oxide (NO) formation; glutathione S-transferases (GSTs);
D O I
10.1097/00005344-200005000-00007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The in vitro study using rats was carried out to clarify the hypothesis that nicorandil is denitrated and then may produce nitric oxide (NO) in myocardial mitochondria. In the presence of a NADPH-generating system, [C-14]nicorandil, which was incubated in mitochondrial and microsomal fractions of the lung, heart, or liver, was converted to its main denitrated metabolite, SG-86 and other metabolites. Apparent K-m and V-max for nicorandil in mitochondrial and microsomal fractions of the heart were considerably similar to those of the lung, bur completely different from those of the liver. It seems that glutathione-S-transferases (GSTs) are not primarily involved in the conversion of nicorandil to SG-86, because a known GST inhibitor, indomethacin, did not affect the nicorandil degradation in the mitochondrial fraction. Nitrite. the stable metabolite of NO, was measured by the Griess reaction. In the presence of an NADPH-generating system, nicorandil significantly increased nitrite production in myocardial mitochondria, but SG-86 did not. These data strongly indicate that nicorandil is metabolized to SG-86 in myocardial mitochondria, then releasing NO, and that GSTs are not primarily responsible for the conversion of nicorandil to SC-86.
引用
收藏
页码:723 / 728
页数:6
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