Cardiac-specific overexpression of GTP cyclohydrolase 1 restores ischaemic preconditioning during hyperglycaemia.

ABSTRACT:

Aims

Hyperglycaemia (HG) decreases intracellular tetrahydrobiopterin (BH(4)) concentrations, and this action may contribute to injury during myocardial ischaemia and reperfusion. We investigated whether increased BH(4) by cardiomyocyte-specific overexpression of the GTP cyclohydrolase (GTPCH) 1 gene rescues myocardial and mitochondrial protection by ischaemic preconditioning (IPC) during HG through a nitric oxide (NO)-dependent pathway.

Methods and results

Mice underwent 30 min of myocardial ischaemia followed by 2 h of reperfusion with or without IPC elicited with four cycles of 5 min ischaemia/5 min of reperfusion in the presence or absence of HG produced by d-glucose. In C57BL/6 wild-type mice, IPC increased myocardial BH(4) and NO concentrations and decreased myocardial

SUBMITTER: Ge ZD 

PROVIDER: S-EPMC3125073 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature