Pharmacological preconditioning in type 2 diabetic rat hearts: the roles of mitochondrial ATP-sensitive potassium channels and the phosphatidylinositol 3-kinase-Akt pathway.
Cardiovasc Drugs Ther
; 23(4): 263-70, 2009 Aug.
Article
en En
| MEDLINE
| ID: mdl-19597978
ABSTRACT
PURPOSE:
The authors examined whether olprinone, a phosphodiesterase type 3 inhibitor, or isoflurane, a volatile anesthetic, could protect the heart against myocardial infarction in type 2 diabetic rats and whether the underlying mechanisms involve protein kinase C (PKC), mitochondrial ATP-sensitive potassium (m-K(ATP)) channels, or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway.METHODS:
All rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Wistar rats received isoflurane or olprinone before ischemia with or without the PKC inhibitor chelerythrine (CHE), the m-K(ATP) channel blocker 5-hydroxydecanoic acid (5HD), or the PI3K-Akt inhibitor LY294002 (LY). Goto-Kakizaki (GK) rats were randomly assigned to receive isoflurane or olprinone. In another group, GK rats received LY before the olprinone.RESULTS:
In the Wistar rats, both isoflurane (38 +/- 11%) and olprinone (40 +/- 11%) reduced infarct size as compared to the control group (59 +/- 8%). In the GK rats, olprinone (41 +/- 9%) but not isoflurane (53 +/- 11%) reduced infarct size as compared to the GK control group (58 +/- 14%). The beneficial effects of olprinone were blocked by LY (58 +/- 14%). In the Wistar rats, CHE, 5HD, and LY prevented isoflurane-induced reductions of infarct size. On the other hand, LY but not CHE or 5HD prevented olprinone-induced reductions of infarct size.CONCLUSIONS:
Olprinone but not isoflurane protects the heart against myocardial infarction in type 2 diabetic rats. The olprinone-induced cardioprotective effect is mediated by the PI3K-Akt pathway but not PKC or m-K(ATP) channels.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Fosfodiesterasa
/
Piridonas
/
Diabetes Mellitus Tipo 2
/
Imidazoles
/
Infarto del Miocardio
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2009
Tipo del documento:
Article