Cardiovascular disease including cardiac hypertrophy is common in patients with kidney disease, and can be partially attenuated using blockers of the renin angiotensin system (RAS). It is unknown whether cardiac microRNAs contribute to pathogenesis of cardiac hypertrophy or to the protective effect of RAS blockade in kidney disease. Using subtotal nephrectomy rat model of kidney injury, we investigated changes in cardiac microRNAs that are known to have direct target genes involved in regulation of apoptosis, fibrosis and hypertrophy. The effect of treatment with the angiotensin converting enzyme inhibitor (ACEi), ramipril on cardiac microRNAs was also investigated. Kidney injury led to a significant increase in cardiac microRNA-212 and microRNA-132 expression. Ramipril reduced cardiac hypertrophy, attenuated the increase in microRNA-212 and microRNA-132 and significantly increased microRNA-133 and microRNA-1 expression. There was altered expression of Caspase-9, B-cell lymphoma 2, transforming growth factor-beta, fibronectin 1, collagen 1a1 and forkhead box proteins O3, all known to be involved in the regulation of apoptosis, fibrosis and hypertrophy in cardiac cells, whilst being targets for the above microRNAs. ACEi treatment increased expression of microRNA-133 and microRNA-1. Inhibitory action of ACEi treatment on increased cardiac NOX1 expression after STNx surgery suggest that inhibition of oxidative stress is also one of mechanism of ACEi mediated cardioprotection. These finding suggests the involvement of microRNAs in the cardioprotective action of ACEi in acute renal injury, which is mediated through an inhibitory action on pro-fibrotic and pro-apoptotic target genes, and stimulatory action on anti-hypertrophic and anti-apoptotic target genes.