Korean J Physiol Pharmacol.  2019 Sep;23(5):329-334. 10.4196/kjpp.2019.23.5.329.

Effect of gemigliptin on cardiac ischemia/reperfusion and spontaneous hypertensive rat models

Affiliations
  • 1Predictive Model Research Center, Korea Institute of Toxicology, Daejeon 34114, Korea. baekeunbok@hanmail.net
  • 2Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • 3Corporate R&D, LG Chem, Ltd., Daejeon 34122, Korea. baekeunbok@hanmail.net
  • 4Department of Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, Korea.

Abstract

Diabetes is associated with an increased risk of cardiovascular complications. Dipeptidyl peptidase-4 (DPP-IV) inhibitors are used clinically to reduce high blood glucose levels as an antidiabetic agent. However, the effect of the DPP-IV inhibitor gemigliptin on ischemia/reperfusion (I/R)-induced myocardial injury and hypertension is unknown. In this study, we assessed the effects and mechanisms of gemigliptin in rat models of myocardial I/R injury and spontaneous hypertension. Gemigliptin (20 and 100 mg/kg/d) or vehicle was administered intragastrically to Sprague-Dawley rats for 4 weeks before induction of I/R injury. Gemigliptin exerted a preventive effect on I/R injury by improving hemodynamic function and reducing infarct size compared to the vehicle control group. Moreover, administration of gemigliptin (0.03% and 0.15%) powder in food for 4 weeks reversed hypertrophy and improved diastolic function in spontaneously hypertensive rats. We report here a novel effect of the gemigliptin on I/R injury and hypertension.

Keyword

Dipeptidyl peptidase-IV; Gemigliptin; Myocardial ischemia-reperfusion injury; Pressure-volume loop; Spontaneously hypertensive rat

MeSH Terms

Animals
Blood Glucose
Hemodynamics
Hypertension
Hypertrophy
Models, Animal*
Rats*
Rats, Inbred SHR
Rats, Sprague-Dawley
Blood Glucose

Figure

  • Fig. 1 Effect of gemigliptin (GG) on ischemia/reperfusion (I/R)-induced infarct size. (A) Change in rat weight as a function of the period of treatment. (B) Representative illustrations of heart sections stained with 2,3,5-triphenyl tetrazolium chloride (TTC). The infarcted area is shown in white color. The white dotted lines indicate the infarcted areas. Six sections cut into 2 mm transverse of the heart to visualize the infarcted areas. (C) Infarct size is quantified as a percentage of total slice area. All data are shown as mean ± standard error of the mean. N = 7–9 hearts per group, Sham vs. I/R, I/R+GG 20, I/R+GG 100 (**p < 0.01; ***p < 0.001), I/R vs. I/R+GG 20, I/R+GG 100 (##p < 0.01; ###p < 0.001).

  • Fig. 2 Effects of gemigliptin (GG) on heart rate and mean blood pressure after ischemia/reperfusion (I/R)-induced injury. (A) HR, heart rate (beats/min); (B) ESP, end-systolic pressure (mmHg); (C) EDP, end-diastolic pressure (mmHg); and (D and E) maximum and minimum dP/dt. All data are shown as mean ± standard error of the mean. N = 7–9 hearts per group, Sham vs. I/R, I/R+GG 20 (GG 20 mg/kg), and I/R+GG 100 (GG 100 mg/kg) rats (**p < 0.01; ***p < 0.001); I/R vs. I/R+GG 20 and I/R+GG 100 (#p < 0.05; ##p < 0.01; ###p < 0.001). NS, not significant.

  • Fig. 3 Effects of gemigliptin (GG) on left ventricular function during ischemia/reperfusion (I/R)-induced injury. (A) ESV, end-systolic volume (µl); (B) EDV, end-diastolic volume (µl); (C) SV, stroke volume (µl); (D) CO, cardiac output (µl); (E) EF, ejection fraction (%); (F) SW, stroke work (mJ); and (G) Representative pressure-volume loop values of sham, I/R, I/R+GG 20 mg/kg, and I/R+GG 100 mg/kg rats. Sham (black), I/R (red), I/R+GG 20 mg/kg (yellow), and I/R+GG 100 mg/kg (green). All data are shown as mean ± standard error of the mean. N = 7–9 hearts per group, Sham vs. I/R, I/R+GG 20, and I/R+GG 100 (**p < 0.01; ***p < 0.001); I/R vs. I/R+GG 20 and I/R+GG 100 (#p < 0.05; ##p < 0.01; ###p < 0.001). NS, not significant.

  • Fig. 4 Effects of gemigliptin (GG) on hemodynamic parameters in spontaneously hypertensive rats (SHR) model. (A) HR, heart rate (beats/min); (B) ESP, endsystolic pressure (mmHg); (C, D) maximum and minimum dP/dt; (E) ESV, end-systolic volume (µl); (F) EF, ejection fraction (%); and (G) Representative pressure-volume loop values of Wistar-Kyoto (WKY), SHR, SHR+GG 0.03 mg/kg, and SHR+GG 0.15 mg/kg rats. WKY (black), SHR (red), SHR+GG 0.03 mg/kg (yellow), and SHR+GG 0.15 mg/kg rats (green). All data are shown as mean ± standard error of the mean. N = 7–9 hearts per group, WKY vs. SHR, SHR+GG 0.03, and SHR+GG 0.15 (*p < 0.05; **p < 0.01; ***p < 0.001); SHR vs. SHR+GG 0.03 and SHR+GG 0.15 (#p < 0.05; ##p < 0.01; ###p < 0.001). NS, not significant.


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