- Background: Heart injury and stress can cause a hypertrophic growth response in cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, and activation of fetal genes, which can lead to heart failure (HF) and death. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we aimed to investigate miRNAs that are regulated during hypertension, left ventricular hypertrophy (LVH) and HF by using a rat model. Methods and Results: Male salt-sensitive (SBH/y) and salt-resistant (SBN/y) Sabra rats were obtained from the Israeli Rat Genome Center. Animals were salt-loaded with deoxycorticosterone-acetate (75 mg DOCA pellet s.c.) and 1% NaCl in drinking water for 16 weeks. Systolic blood pressure was determined by the tail-cuff method. Cardiac images were obtained using cardiac MRI using a specific small animal imaging protocol. Rats were sacrificed at different time points. miRNA expression was studied in the left ventricle using GeneChip miRNA Array (affymetrix). Expression of miRNAs related to cardiac hypertrophy or cell proliferation, including miR-132, miR-212, miR-29, miR-31and miR-205, increased more than 1.5 fold in salt-loaded SBH/y compared with salt-loaded SBN/y. In contrast, expression of MiR-182, miR-17-3p and miR-130b, known to be down-regulated in heart disease, diminished more than -1.5 fold in salt-loaded SBH/y compared with salt-loaded SBN/y. Conclusions: In animal model of salt-sensitive hypertension and LVH, up- and down-regulation of distinct miRNAs in the heart suggest novel therapeutic targets to prevent and reverse LVH and HF.