Abstract 533: Effect of Dipeptidyl Peptidase-4 Inhibition on Blood Pressure and Its Dipping Pattern in Dahl Salt-Sensitive Rats

Abstract

Several studies have indicated that treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors decreases blood pressure. We aimed to examine the effects of vildagliptin, a specific DPP-4 inhibitor, on blood pressure and its dipping pattern in Dahl salt-sensitive (DSS) rats. Male DSS rats were treated with a high salt (8% NaCl) diet and vehicle (0.5% carboxymethylcellulose) or vildagliptin (3 or 10 mg/kg, twice daily, p.o.) for 7 days (n = 7 per group). Mean arterial pressure (MAP) was measured by telemetry. High salt diet for 7 days significantly increased MAP with an extreme dipping pattern of blood pressure in DSS rats. Vildagliptin dose-dependently inhibited DPP-4 enzymatic activity and increased plasma GLP-1 levels. Furthermore, vildagliptin dose-dependently attenuated the development of salt-induced hypertension. Interestingly, vildagliptin significantly increased urine sodium excretion and normalized the dipping pattern. In anesthetized high salt-diet DSS rats, acute intra-cerebroventricular infusion of vildagliptin (50, 500 or 2500 μg in 10 μl solution) did not alter MAP or heart rate (n = 4). These data suggest that treatment with the DPP-4 inhibitor, vildagliptin, attenuates the extreme dipping pattern of blood pressure and development of salt sensitive hypertension by increasing urinary sodium excretion. These effects of vildagliptin may not be mediated through the central nervous system.