Isoflurane Preconditioning Modulates the Expression of eNOS and eNOS‐related Genes during Myocardial Ischemia and Reperfusion

Endothelial nitric oxide synthase (eNOS) contributes to isoflurane preconditioning (IsoPC), a form of pharmacological cardioprotection against ischemia‐reperfusion injury. We investigated the effects of IsoPC on the expression of eNOS and eNOS‐related genes: GTP cyclohydrolase‐1 (GTPCH‐1), dimethylaminohydrolase‐2 (DDAH‐2), and protein arginine N‐methyltransferase‐1 (PRMT‐1) during myocardial ischemia and reperfusion. Rats were preconditioned with 1.4% isoflurane administered for 30 min followed by discontinuation for 15 min prior to occlusion of the left anterior descending coronary artery for 30 min. Gene expression in cardiac tissue was quantified by real‐time PCR at five time points: pre‐occlusion, occlusion, 30, 60 and 90 min of reperfusion. Expression of all genes decreased during occlusion and reperfusion in control animals. Isoflurane alone decreased gene expression before coronary artery occlusion, but conversely, attenuated further decreases in gene expression that were observed during occlusion and reperfusion in control rats. Expression of GTPCH‐1, DDAH‐2 and PRMT‐1 recovered to baseline values and eNOS expression was increased after 60 min of reperfusion in the IsoPC compared to the control group. This suggests that IsoPC exerts time‐dependent changes in genes expression pattern that may influence the function of eNOS during and after myocardial ischemia‐reperfusion injury.