ObjectiveTo establish heart-specific (pro)renin receptor ［(p)RR］ transgenic mice and investigate its regulation effect on the process of cardiomyopathy. Methods The transgenic vector was constructed by inserting the human (p)RR cDNA sequence into the down-stream of α-MHC promoter. The transgenic mice were generated by the method of microinjection. The genotype of transgenic lines was identified by PCR, and the expression levels of the (p)RR gene were detected by Western Blot and immunohistochemistry. The cardiac geometry and function were detected by echocardiography. Subcellular localization of (p)RR was performed by double immunofluorescence confocal staining. At last, we detected the expression level of ATP2A2, NCX1 and cTnT via Western Blot. ResultsThe heart-specific (p)RR transgenic mice were established and one high-level expression line was identified. Endogenous and transgenic (p)RR were located in the Golgi body and endoplasmic reticulum. Overexpression (p)RR with heart-specific resulted in enhancing contractile properties. Compared with the wild type mice, transgenic mice left ventricular systolic diameter decreased by 9% (P 〈0.05, n=18), left ventricular end-systolic volume reduced by 23% (P 〈0.05, n=18), ejection fraction increased by 14% (P 〈0.01, n=18) and fraction shortening elevated by 20% (P 〈0.01, n=18). The expression level of the proteins involving in Ca²⁺ and contractile properties were altered, SRECA and NCX1 decreasing, while cTnT increasing. Conclusion Over-expression of (p)RR in the heart of the transgenic mice leaded to significantly enhanced cardiac contractile properties., and while regulated the expression of SRECA, NCX1 and cTnT, directly or indirectly. These results indicated (p)RR participated in influencing cardiac function via regulating the Ca²⁺ of the myocardium.