Journal
CIRCULATION JOURNAL
Volume 73, Issue 3, Pages 554-561Publisher
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-08-0843
Keywords
Mitochondria; Oxygen radicals; Platelets; Thrombosis
Categories
Funding
- Ministry of Education. Culture, Sports. Science and Technology of Japan [20590888]
- Tokai University School of Medicine
- Grants-in-Aid for Scientific Research [20590888] Funding Source: KAKEN
Ask authors/readers for more resources
Background: Although nicorandil has a number of beneficial cardiovascular actions, its effects on endothelial cells in the context of thrombosis have not been elucidated. Methods and Results: Arterial thrombosis was induced by endothelial injury caused by FeCl3 in the mouse testicular artery. Thrombus growth led to complete occlusion 12 min after endothelial injury in control mice. The antiplatelet agent, tirofiban, and nicorandil significantly slowed the growth of thrombi, resulting in arterial occlusion after 58 min and 55 min, respectively. In the absence of endothelial cells, nicorandil did not inhibit platelet aggregation. Diazoxide and high-dose isosorbide dinitrate both showed a similar effect to that of nicorandil. The beneficial effect of nicorandil was prevented by 5-hydroxydecanoate, but not by L-NAME. The production of reactive oxygen species by FeCl3 treatment was measured with the specific fluorescent probe, dihydrorhodamine 123. After FeCl3 treatment, nicorandil significantly inhibited the increase in fluorescence. In further experiments, incubation of human umbilical vein endothelial cells with nicorandil did not change the endothelial nitric oxide synthase (eNOS) mRNA levels, eNOS phosphorylation or nitrite production. Conclusions: Nicorandil attenuates FeCl3-induced thrombus formation in the mouse testicular artery, which suggests that it may inhibit the generation of reactive oxygen species by FeCl3-treated endothelial cells through activation of the mitochondrial ATP-sensitive potassium channels. (Circ J 2009; 73: 554-561)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available