Glucose metabolism in the heart requires oxidation of cytosolic NADH from glycolysis. This study examines shuttling reducing equivalents from the cytosol to the mitochondria via the activity and expression of the oxoglutarate-malate carrier (OMC), in rat hearts subjected to 2 (HYP2, n=6) and 10 weeks (HYP10, n=8) of pressure overload vs. that of sham-operated rats (SHAM2, n=6 and SHAM10, n=7). Moderate aortic banding produced increased atrial natriuretic factor (ANF) mRNA expression at 2 and 10 weeks, but only at 10 weeks did hearts develop compensatory hypertrophy (33% increase, P<0.05). Isolated hearts were perfused with the short chain fatty acid, [2,4-13C2] butyrate (2 mM) and glucose (5 mM) to enable dynamic-mode 13C NMR of intermediate exchange across OMC. OMC flux increased prior to development of hypertrophy: HYP2 = 9.6 ±2.1 micromole/min/g dw vs. SHAM2 = 3.7 ± 1.2 providing an increased contribution of cytosolic NADH to energy synthesis in the mitochondria. With compensatory hypertrophy, OMC flux returned to normal: HYP10 = 3.9 ± 1.7 micromole/g/min vs. SHAM10 = 3.8 ±1.2. Despite changes in activity, no differences in OMC expression occurred between HYP and SHAM. Elevated OMC flux represented augmented cytosolic NADH shuttling, coupled to increased nonoxidative glycolysis, in response to hypertrophic stimulus. However, development of compensatory hypertrophy moderated the pressure-induced elevation in OMC flux, which returned to control levels. The findings indicate that the challenge of pressure overload increases cytosolic redox state and its contribution to mitochondrial oxidation, but that hypertrophy, prior to decompensation, alleviates this stress response.