Sitagliptin Modulates the Electrical and Mechanical Characteristics of Pulmonary Vein and Atrium.

BACKGROUND The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs. METHODS Conventional microelectrodes were used to record the action potentials (APs) in isolated PVs, right atrium (RA), and left atrium (LA) in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without sitagliptin (10 mg/kg) for 4 weeks. RESULTS WKY (n = 5), SHR (n = 7), sitagliptin-treated WKY (n = 5) and sitagliptin-treated SHR (n = 7) had similar PV or sinoatrial spontaneous beating rates. However, the sitagliptin-treated WKY had fewer sinoatrial-PV beating rate differences than WKY, SHR or sitagliptin-treated SHR. WKY and SHR had shorter 90% (APD90) of RA AP duration than sitagliptin-treated WKY or sitagliptin-treated SHR. In contrast, WKY had longer LA APD90 than sitagliptin- treated WKY, but SHR and sitagliptin-treated SHR had similar LA APD90. Sitagliptin-treated WKY or sitagliptin- treated SHR had larger (RA-LA) APD90 differences than WKY or SHR, respectively. Moreover, as compared to WKY the post-rest potentiation of contraction was decreased in SHR, sitagliptin-treated WKY, and sitagliptin-treated SHR. CONCLUSIONS Sitagliptin significantly affects the electromechanical characteristics of PVs and atria, which can be modulated by hypertension. KEY WORDS Atrial fibrillation; Atrium; Dipeptidyl peptidase inhibitor-4; Hypertension; Pulmonary vein.