High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels

作者：Ichinomiya Taiga; Cho Sungsam^*; Higashijima Ushio; Matsumoto Shuhei; Maekawa Takuji; Sumikawa Koji

来源：Cardiovascular Diabetology, 2012, 11: 28.

DOI：10.1186/1475-2840-11-28

• Hyperglycemia
• Postconditioning
• Myocardial Infarction
• Fasudil
• Mitochondrial KATP channels

Background: The current study was carried out to determine whether fasudil hydrochloride (fasudil), a Rho-kinase inhibitor, has myocardial postconditioning (PostC) activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP) channels. %26lt;br%26gt;Methods: Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg) or high-dose (0.5 mg/kg) fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD), an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR). %26lt;br%26gt;Results: Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 +/- 8%, 21 +/- 9% and 21 +/- 10% of AAR, respectively) compared with that in the control (42 +/- 7%). Under hyperglycemia, low-dose fasudil (40 +/- 11%) and diazoxide (44 +/- 14%) could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 +/- 13%). 5HD prevented fasudil-induced reduction of myocardial infarct size (42 +/- 13%). %26lt;br%26gt;Conclusion: Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.

• 出版日期2012-3-22