Dipeptidyl Peptidase IV Inhibition Ameliorates Cardiorenal Function in Experimental Heart Failure (701.9)

We have recently reported that long‐term dypeptidyl peptidase IV (DPPIV) inhibition mitigates the development and/or progression of HF in rats subjected to myocardial injury. The present study aimed to investigate whether the DPPIV inhibitor vildagliptin is capable of improving cardiorenal function in rats with established heart failure. Experimental HF was induced in male Wistar rats via left ventricular (LV) myocardial injury using radiofrequency catheter ablation. Sham‐operated rats underwent left thoracotomy and were mock‐ablated. Echocardiographic analysis were performed six (Phase I) and ten (Phase II) weeks after surgery. After the Phase I analysis, HF rats were randomly divided into four groups and treated with vildagliptin (VIL) at daily doses of 20, 80 or 120 mg/kg of body weight or vehicle. Compared to Phase I, Phase II LV ejection fraction reduced in HF groups treated with water or VIL20, remained unaltered in HF rats treated with VIL80 and increased in rats treated with the higher dose of vildagliptin, VIL120. All vitagliptin‐treated rats exhibited lower lung water content and heart weight to body weight ratio as compared to HF rats treated with water. Treatment with VIL80 and VIL120 remarkably reduced BNP circulating levels as compared to vehicle treated HF rats (167±40 and 152±42 vs. 372±75 pg/mL, respectively). HF rats displayed sodium retention and lower glomerular filtration rate compared to Sham. Treatment with VIL120 was capable of restoring renal function in HF rats. Taken together, these results suggest that DPPIV inhibition improves cardiorenal function in rats with established HF. Thus, DPPIV inhibitors may be effective not only for the prevention but also for the treatment of HF in rats.Grant Funding Source: Supported by FAPESP.