Hypertension induced by high salt diet in Dahl salt-sensitive rats leads to compensatory cardiac hypertrophy by ~11 weeks, cardiac dysfunction at ~17 weeks and death from cardiac dysfunction at ~21 weeks. It is unclear what molecular hallmarks distinguish the compensatory hypertrophy from the decompensated cardiac dysfunction phase. Here, we compared gene expression in rat cardiac tissue from the compensatory hypertrophic phase (11 weeks, n=6), with the cardiac dysfunction phase (17 weeks, n=6) and with age-matched normotensive controls. Messenger RNA levels of 93 genes, selected based on predicted association with cardiac dysfunction, were measured by quantitative Real-Time PCR. In the hypertrophic phase, the expression of three genes, atrial natriuretic peptide (ANP, p=0.0089), brain natriuretic peptide (p=0.0012) and endothelin-1 precursor (p=0.028), significantly increased, whereas there was decreased expression of 24 other genes including SOD2, (p=0.0148), SERCA2a, (p=0.0002) and ryanodine receptor 2 (p=0.0319). In the subsequent heart cardiac dysfunction phase, the expression of an additional 20 genes, including iNOS (p=0.0135), angiotensin I converting enzyme (p=0.0082) and IL-1 (p<0.0001), increased whereas the expression of seven genes decreased, as compared with age-matched controls. Further, the expression of 22 genes, including prepro-endothelin-1, ANP, angiotensin I converting enzyme, 1-adrenergic receptor, SOD2 and eNOS, significantly changed in the cardiac dysfunction phase as compared with the compensatory hypertrophic phase. Finally, principal component analysis successfully segregated animals with decompensatory cardiac dysfunction from controls, as well as from animals at the compensated hypertrophy phase, suggesting that we have identified molecular markers for each stage of the disease.