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.


BACKGROUND
Atrial fibrillation; Atrium; Dipeptidyl peptidase inhibitor-4; Hypertension; Pulmonary vein.
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; ; Division of Cardiology, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan;
Chien-Jung
CJ
Chang
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; ; Division of Cardiovascular Medicine, Department of Internal Medicine, Taipei Medical University and Hospital, Taipei, Taiwan;
Ten-Fang
TF
Yang
Division of Endocrinology and Metabolism, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;
Tin-I
TI
Lee
Department of Biomedical Engineering and Institute of Physiology, National Defense Medical Center, Taipei, Taiwan;
Yao-Chang
YC
Chen
Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; ; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;
Yu-Hsun
YH
Kao
Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospital, Taipei, Taiwan;
Shih-Ann
SA
Chen
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; ; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Yi-Jen
YJ
Chen