Ischemia/reperfusion has been associated with ventricular (LV) remodeling, including induction of interstitial fibrosis, cardiomyocyte apoptosis, and hypertrophy. Cardiac hypertrophy is a compensatory process which occurs in pathological conditions, such as hypertension, myocardial infarction, and some genetic heart diseases. 慣1-Adrenoceptors (ARs) have been implicated in the pathogenesis of cardiac hypertrophy, ischemia-induced cardiac arrythmias and ischemic preconditioning. The goal of the present study is to test the hypothesis that 慣1-AR-mediated hypertrophy is selectively mediated via the oxidative modification of Gh during hypoxia/reoxygenation or ischemia/reperfusion. To perform this work, we first examined whether 慣1-AR mainly mediated hypertrophic response in norepinephrine (NE)-stimulated neonatal cardiomyocytes using the 慣1selective antagonist, prazocin. The increases in protein/DNA ratio and extracellular signal-regulated kinases (ERKs) phosphorylation as an index for the hypertrophic phenotype were observed in this experiment. Reactive oxygen species (ROS) production as a stimulator was also increased in hypoxia/reoxygenation (H/R). The mRNA levels of 慣1-adrenoceptors in hypertrophic responses in both in vivo model of I/R myocardium and in vitro model of H/R cardiomyocytes were not increased but mRNA level of Gh protein was significantly increased. To further address the involvement of Gh in hypertrophic response of NE-stimulated cardiomyocytes, specific relation of Gh was confirmed by using Gh overexpression and inhibition into cardiomyocytes. Also mainly increased membrane Gh protein by ROS stimulation has a more sensitive effect on myocardial hypertrophy through MEK1,2/ERKs signal transduction pathway regardless of PLC 灌1 and induction of proto-oncogene, c-fos by 慣1-AR in neonatal cardiomyocytes. These results provide that ROS production by I/R mediates Gh protein increase and increased Gh protein leads to more specific responsiveness to NE stimulated-hypertrophy in neonatal cardiomyocytes.