Teneligliptin Prevents Cardiomyocyte Hypertrophy, Fibrosis, and Development of Hypertensive Heart Failure in Dahl Salt-Sensitive Rats

J Card Fail. 2018 Jan;24(1):53-60. doi: 10.1016/j.cardfail.2017.09.001. Epub 2017 Sep 6.

Abstract

Background: We investigated the effects of the dipeptidyl peptidase 4 inhibitor teneligliptin on cardiac function and hemodynamics during heart failure in hypertensive model rats.

Methods and results: Fifty-five male Dahl salt-sensitive rats were divided into 4 groups: control group (0.3% NaCl chow; n = 13), hypertension (HT) group (8% NaCl chow; n = 20), HT-early TNL group (8% NaCl chow and teneligliptin from 6 weeks; n = 10), and HT-late TNL group (8% NaCl chow and teneligliptin from 10 weeks; n = 12). Hemodynamic measurement and tissue analyses were performed at 18 weeks. In all of the HT groups, systolic blood pressures were similarly elevated (P = .66) and heart weights similarly increased (P = .36) with and without TNL administration. LV end-diastolic dimension was significantly enlarged only in the HT-early TNL group compared with the control group (P = .025). Histologic analysis showed less fibrosis (P = .008) and cardiomyocyte widths (P = .009) in the HT-early TNL group compared with the HT group. On hemodynamic analysis, only the HT group showed significant LV end-diastolic pressure elevation (P = .049) and lung congestion (P < .001) compared with the control group.

Conclusions: These results suggest that teneligliptin prevents concentric LV hypertrophy, fibrosis, and development of congestive heart failure in Dahl salt-sensitive rats. Teneligliptin may inhibit pressure-overload hypertrophic adaption and result in LV eccentric hypertrophy with reduced LV ejection fraction.

Keywords: Dipeptidyl peptidase 4 inhibitors; fibrosis; heart failure with preserved ejection fraction; myocardial hypertrophy.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Dipeptidyl-Peptidase IV Inhibitors
  • Disease Models, Animal
  • Fibrosis / complications
  • Fibrosis / pathology
  • Fibrosis / prevention & control
  • Heart Failure / drug therapy*
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Hypertension / complications
  • Hypertension / physiopathology
  • Hypertension / prevention & control*
  • Hypertrophy, Left Ventricular / complications
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / prevention & control*
  • Male
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology*
  • Pyrazoles / therapeutic use*
  • Rats
  • Rats, Inbred Dahl
  • Thiazolidines / therapeutic use*
  • Treatment Outcome
  • Ventricular Function, Left / drug effects

Substances

  • 3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine
  • Dipeptidyl-Peptidase IV Inhibitors
  • Pyrazoles
  • Thiazolidines