The renin-overproducing transgenic rat (mREN2) has recently been proposed as a model of left ventricular (LV) hypertension and fibrosis. Comparing mREN2 (n=7) to sex- and age-matched Wistar-Han control rats (WHAN, n=11), we have confirmed hypertension (mean blood pressure: 174±9 vs. 107±3 mmHg, P<0.001), hypertrophy (LV weight:body weight: 4.0±0.1 vs. 2.7±0.1 mg/g, P<0.001), and cardiac fibrosis. At the protein level, LV from mREN2 exhibited significantly higher percentage of interstitial collagen per total protein area versus WHAN (5.95±1.01% vs. 1.96±0.06%, P=0.02). At the level of LV function, mREN2 hearts demonstrated significant diastolic dysfunction (increased stiffness coefficient from stress-strain relationship: 198±30 vs. 78±10, P=0.01, and reduced magnitude of dP/dtmin: 1254±125 vs. 2000±110 mmHg/s, P<0.001), and impaired relaxation (increased relaxation time constant: 0.048±0.001 vs. 0.043±0.001 s, P=0.002). The naturally occurring hormone relaxin is known to have antifibrotic properties in multiple organ systems and it affects both synthesis and degradation aspects of collagen homeostasis. It is known that relaxin (RLN1) and receptor (RXFP1) are expressed locally in LV tissue, yet the biological function of the endogenous relaxin message-receptor system is not fully understood. Interestingly, the relative mRNA expressions of relaxin and relaxin receptor were increased in this model of LV fibrosis (2-ΔΔCT by qRT-PCR for RLN1: 3.04±0.56 (mREN2) vs. 1.0±0.18 (WHAN), P=0.001; and RFXP1: 7.06±1.57 (mREN2) vs. 1.00±0.20 (WHAN), P=0.003). Thus, the unregulated endogenous relaxin-receptor system in the mREN2 fibrosis model seems to be an adaptive response which is trying to keep the fibrosis in check. However, this endogenous adaptive response is insufficient to completely block collagen accumulation and prevent LV diastolic dysfunction. We are currently conducting experiments to examine whether exogenous administration of relaxin can assist the endogenous adaptive response and reverse LV fibrosis and normalize diastolic function in this model.