Primary hyperaldosteronism patients develop cardiac injury and dysfunction. In animal experimental models, excess aldosterone (ALDO) only causes cardiac injury in the presence of high salt (HS) intake. To study which molecular mechanisms are involved ALDO/HS‐mediated cardiac injury and its dependence on HS intake, we studied cardiac whole genome gene expression (GE). Male Sprague Dawley rats (n=6 per group) were uninephrectomized, and treated with ALDO (0.75 μg/h delivered by miniosmotic pumps), 0.9 % NaCl in the drinking water or a combination of both of them for 2 days, or 1, 2, 4 or 8 wks. Whole genome GE was performed using Illumina Beadarrays and GE was analyzed using GeneSpring software. ALDO/HS caused severe left ventricle GE changes after only 2 wks of treatment. Although either ALDO or HS alone changed GE (209 and 289 genes, respectively) the combination synergistically modified the expression of 1046 genes (493 UP and 553 DOWN). Bioinformatics analysis indicate that the Gene Ontology set of inflammatory response genes (n=17) and genes with the Sp1 transcription factor binding site in their promoter are significantly enriched. Similar GE results were observed after 4 and 8 wks of treatment. In summary, we report a left ventricle time series GE analysis in an animal experimental model of ALDO‐mediated cardiac injury highlighting many new genes involved in this pathological condition.