The effects of leptin on cardiac function in streptozotocin diabetic rats

E. Arioglu Inan¹, G. Kayki Mutlu¹, B. R. Erdogan¹, A. E. Muderrisoglu¹, I. Karaomerlioglu¹, Z. E. Yesilyurt¹, S. Degirmenci², B. Turan², V. M. Altan³. ¹Pharmacology, Ankara University, Ankara, Turkey, ²Biophysics, Ankara University, Ankara, Turkey, ³Pharmacology, Bezmi Alem Vakif University, Istanbul, Turkey.

Introduction: Leptin, a hormon secreted from white adipose tissue, has been reported to have role in the regulation of cardiac contractility (1). In the present study, we aimed to investigate the effects of leptin on streptozotocin (STZ) diabetic rat heart.

Method: 10-week old Sprague Dawley rats were divided into 3 groups.; control (C), diabetic (D), leptin treated diabetic (L). Diabetes was induced by streptozotocin injection (40mg/kg, i.p.). Leptin treatment was made via minipump (300ug/kg/day, 14 days). Cardiac parameters were evaluated by PV loop analysis, Langendorff heart preparation, histological examination and through intracellular Ca++ levels/Ca++ transients under either isofluoran or ketamin/xylazine anesthesia.

Results: Leptin treatment ameliorated most of the basal hemodynamic parameters such as end systolic pressure (C:111±1.5, D:78±2.3, L:99±1.4, p<0.001 vs C and vs D), rate of contraction (C:8059±169, D:4067±209, L:6357±209, p<0.001 vs C and vs D), rate of relaxation (C:6751±171, D:3193±143, L:5444±184, p<0.001 vs C and p<0.05 vs D), isovolumic relaxation constant (C:10.51±0.23, D:17.68±0.39, L:10.98±0.71, p<0.001 vs C and D), cardiac stiffness (C: 0.0065±0.0008, D:0.0160±0.0036, L:0.0050±0.0005, p<0.01 vs C, p<0.001 vs D) and preload recruitable stroke work (C:61.54±4.12, D:45.68±1.18, L:60.82±3.10, p<0.01 vs C and vs D) (n=7-8). Beta 1 AR mediated contractile reponses were restored in L group (emax at 0.1μM, C: %191.10±16.51; D, %147.2±11.49; L, %195.2±10.8, p<0.05 vs C, p<0.01 vs D) (n=4-5). Beta 3 AR mediated relaxation response was increased in D group and not improved in L group (emax at 1μM, C: %94.28±5.38; D, %83.05±3.85; L, %82.79±12.8, p<0.05 vs C) (n=6-8). Although basal intracellular Ca⁺² levels were not different among groups (C: 0.615±0.01; D: 0.611±0.03; L:0.616±0.006, ns), Ca⁺² transients and SR Ca⁺² loading were found to be decreased in D group (Ca⁺⁺ transients; C: 0.419±0.06; D: 0.191±0.02; L:0.279±0.01 p<0.01 vs C, SR Ca⁺⁺ loading; C: 0.386±0.02; D: 0.305±0.01; L:0.33±0.01 p<0.05 vs C) (n=5). Leptin treatment partially restored these parameters. Cardiomyocyte width was increased in D group and improved in L group (C: 12.76 ± 0.88; D: 14.91 ± 0.75; L: 13.80 ± 1.289, p<0.01 vs C and vs D). Collagen deposition was increased in D group and decreased after leptin treatment (C: 1.390 ± 0.355; D: 3.356 ± 0.593; L: 2.033 ± 0.505, p<0.01 vs C and vs D) (n=5).

Conclusions: These results indicate that leptin treatment changes most of the cardiac parameters in STZ diabetic rat.

References:

1.Karmazyn M et al. (2008). Cardivascular Research, 79:279-286.