alogliptin and Tachycardia--Ventricular

Dipeptidyl peptidase-4 (DPP-4) inhibitors were recently reported to have cardioprotective effects via amelioration of ventricular function. However, the role of DPP-4 inhibition in atrial remodeling, especially of the arrhythmogenic substrate, remains unclear.. We investigated the effects of a DPP-4 inhibitor, alogliptin, on atrial fibrillation (AF) in a rabbit model of heart failure caused by ventricular tachypacing (VTP).. Rabbits subjected to VTP at 380 bpm for 1 or 3 weeks, with or without alogliptin treatment, were assessed using echocardiography, electrophysiology, histology, and immunoblotting and compared with nonpaced animals.. VTP rabbits exhibited increased duration of atrial burst pacing-induced AF, whereas administration of alogliptin shortened this duration by 73%. The extent of atrial fibrosis after VTP was reduced by 39% in the alogliptin-treated group. VTP rabbits treated with alogliptin displayed a 1.6-fold increase in left atrial myocardial capillary density compared with nontreated rabbits. A 2-fold increase in endothelial nitric oxide synthase (eNOS) phosphorylation was observed in the left atrium of alogliptin-treated rabbits compared with nontreated rabbits. Moreover, a nitric oxide synthase inhibitor (N(ω)-nitro-l-arginine methyl ester) blocked the beneficial effects of alogliptin on AF duration, fibrosis, and capillary density.. Alogliptin shortened the duration of AF caused by VTP-induced fibrotic atrial tissue by augmenting atrial angiogenesis and activating eNOS. Our findings suggest that DPP-4 inhibitors may be useful in the prevention of heart failure-induced AF.

Topics: Animals; Atrial Fibrillation; Blotting, Western; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Echocardiography; Electrophysiology; Endothelium; Enzyme-Linked Immunosorbent Assay; Fibrosis; Fluorescent Antibody Technique; Heart Atria; Heart Failure; Male; Neovascularization, Physiologic; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Phosphorylation; Piperidines; Rabbits; Tachycardia, Ventricular; Uracil