Back to Search
Start Over
High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels
- Source :
- Cardiovascular Diabetology, Cardiovascular Diabetology, Vol 11, Iss 1, p 28 (2012)
- Publication Year :
- 2012
- Publisher :
- BioMed Central, 2012.
-
Abstract
- 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.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).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%).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.<br />Cardiovascular Diabetology, 11(28), pp.1-9; 2012
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
lcsh:Diseases of the circulatory (Cardiovascular) system
Mitochondrial KATP channels
Potassium Channels
Endocrinology, Diabetes and Metabolism
Myocardial Infarction
Myocardial Reperfusion Injury
Postconditioning
Rats, Sprague-Dawley
Internal medicine
Diabetes mellitus
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Fasudil
medicine
Diazoxide
Animals
Channel blocker
Myocardial infarction
Protein Kinase Inhibitors
Original Investigation
Cardioprotection
Dose-Response Relationship, Drug
business.industry
medicine.disease
Rats
Dose–response relationship
lcsh:RC666-701
Hyperglycemia
Ischemic Preconditioning, Myocardial
Models, Animal
Cardiology
Ischemic preconditioning
Cardiology and Cardiovascular Medicine
business
Hydroxy Acids
Decanoic Acids
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 14752840
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Diabetology
- Accession number :
- edsair.doi.dedup.....e07ff36a36f5df29ced7338a67957495