Abstract 079: Dipeptidyl Peptidase IV (DPP4) Inhibition Enhances the Vasoconstrictor Response to Neuropeptide Y During Angiotensin-converting Enzyme Inhibition

Abstract

Background: Dipeptidyl peptidase IV (DPP4) inhibitors are antidiabetic medications that may increase risk of heart failure. Neuropeptide Y (NPY), a substrate of DPP4, is co-released with norepinephrine (NE) and causes vasoconstriction via the Y1 receptor. We tested the hypothesis that DPP4 inhibition would potentiate the effect of exogenous NPY on forearm blood flow (FBF). Methods: Seven healthy non-smokers participated in a randomized, double-blinded, placebo-controlled crossover study. Subjects underwent two study days and received sitagliptin 100 mg daily or placebo for seven days before each study day. On each study day, NPY was infused at 0.1, 0.3, 1.0, and 3.0 nmol/min through the brachial artery and FBF was measured using plethysmography. Following 90-minute washout, subjects received intra-arterial enalaprilat and NPY infusion was repeated. Venous and arterial samples were obtained for NE and NPY. Results: FBF decreased to a similar extent with increasing doses of NPY during sitagliptin and placebo (Figure 1). During enalaprilat, sitagliptin potentiated the vasoconstrictor effect of NPY compared to placebo (FBF 1.32 vs 1.94 mL/min/100mL at 0.3 nmol/min NPY during sitagliptin and placebo, respectively, P=0.039, Figure 1). NE decreased with ACE inhibition during NPY infusion, but this effect was not altered by DPP4 inhibition (Change in NE -47 vs -66 pg/mL with sitagliptin and placebo, respectively, P=0.92). Conclusion: DPP4 inhibition potentiates the vasoconstrictor effect of NPY in the forearm vasculature in the setting of ACE inhibition. These findings have implications for the cardiovascular effects of DPP4 inhibitors in patients receiving ACE inhibitors.