Cardiac hypertrophy carries a risk of heart failure and sudden cardiac death, and is a growing health problem because of the increasing prevalence of hypertension in the aging population. MicroRNAs show great promise as therapeutic agents and targets in disease treatment. Maximising their therapeutic potential for heart disease requires an understanding of the effects of microRNAs on target genes that influence cardiac function. Important among these are inward rectifier potassium channels that are downregulated in cardiac hypertrophy, increasing the risk of sudden death from cardiac arrhythmia. Reduction of inward rectifier current enhances delayed afterdepolarisations, thereby increasing the risk of extrasystoles and consequent fatal ventricular arrhythmias1. Several cardiac microRNAs are known or predicted to target cardiac inward rectifier genes (KCNJ2 and KCNJ12), and therefore may be useful therapeutic targets, especially at early stages of the disease. Using next-generation sequencing, we aimed to determine the changes in these cardiac microRNAs in spontaneously hypertensive, heart failure prone (SHHF) rats at 8 months of age, when cardiac hypertrophy is at an early stage2 and inward rectifier current is reduced3. Small RNA was isolated from the left ventricles of SHHF and Wistar-Furth (WF, control) rats. cDNA libraries were prepared with separate barcodes, combined, and sequenced on an Illumina MiSeq (TrinSeq, Trinity College, Dublin). Results were analysed with CLC Genomics Workbench v4.0, and showed upregulation of miR-212 (WF 4.91±1.68, SHHF 11.50±2.63), miR-143 (WF 170518.6±31331.3, SHHF 271996.9±36074.7), miR-146b (WF 465.19±203.77, SHHF 1818.02±528.18), miR-194 (WF 78.45±25.10, SHHF 143.68±20.89) and miR-218a (WF 38.79±5.33, SHHF 87.43±16.49) (all p<.05, Baggerley’s test4), and no change of miR-1 (WF 5795.37±897.55, SHHF 8440.72±4593.01) and miR-26a (WF 140463.6±6417.84, SHHF 124698.2±9409.3) (mean±sem reads per million mapped; n = 4 SHHF, 5 WF). Inward rectifier current density is further reduced at 17 months of age in SHHF rats3, by which time a decrease in Kir2.1 protein is detectable. Western blots of left ventricular myocardial tissue from 4 WF and 4 SHHF 17-month-old rats showed reduced expression of Kir2.1 protein (WF 0.239±0.0257; SHHF 0.135±0.0373; p<.05; relative to HPRT1 loading control; t-test). These results identify several microRNAs as potential targets for prevention of inward rectifier downregulation, and reducing the risk of arrhythmia and sudden cardiac death.