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Effects of carbohydrate and fat rich food and antidiabetic treatment on vasorelaxation in aortas of obese pre-diabetic elderly rats

Introduction: Previously, we have demonstratedsex- related and antidiabetic drugs-relateddifferences in the level of oxidative stress and antioxidative enzymes activityinaortas of treated obese prediabetic elderly rats (HSHFD), and that drugs may modify antioxidative capacity more prominent in female rats.This study aimed to evaluate vasccular function, acetylcholine induced relaxation (AChIR) in HSHFD rats. Methods:Spraque-Dawley (SD) rats (Ntotal=52), both sexes, were divided in control group (fed standard rat food) ; HSHFD group fed carbohydrate and fat rich food from 20-65 weeks of age ; HSHFD+metformin treatment (50 mg/kg/day s.c.) and HSHFD+liraglutide treatment (0.3 mg/kg/day s.c). Anesthetized rats (combination of ketamine (75 mg/kg) and midazolam (2.5 mg/kg)) were decapitated, thoracic aorta was isolated and used to test AchIR in the absence/presence of NO-synthase inhibitor L-NAME (10- 6M) or superoxide scavenger TEMPOL(10-5M). Two-way ANOVA was used to test differences (GraphPad Prism v5.0). p<0.05 was significant. Results:AChIR was reduced in HSHFD+METFORMIN(female) group compared to CONTROL(female). HSHFD(female) group exhibited lower sensitivity to ACh than HSHFD+METFORMIN(female) group. CONTROL(male) group exhibited reduced baseline AChIR compared to all other male groups. Sensitivity to ACh in the presence of TEMPOL was decreased in CONTROL(male) group compared to others. HSHFD+METFORMIN(male)and HSHFD+LIRAGLUTID(male) rats had better AChIR compared to HSHFD(male) group. In all male groups, L-NAME abolished, while TEMPOL did not influence AChIR.Also, aortic rings sensitivity to ACh in presence of L-NAME was significantly increased compared to sensitivity on ACh in presence of TEMPOLin HSHFD(male) and HSHFD+METFORMIN(male). CONTROL(male) exhibited reduced AChIR compared to CONTROL(female) rats. HSHFD+METFORMIN(male) rats had reduced AChIR compared to HSHFD+METFORMIN(female) rats. Discussion:In all groups of rats, both sexes, NO mediated AChIR. TEMPOL restored AChIR in CONTROL(female) group to the baseline values, in contrast to CONTROL(male) group where TEMPOL alleviated AchIRcompared to other groups. Conclusion: Present results, together with previous ones, suggest that better oxidative status in a female group leads to minor changes in vasorelaxation. Aged male rats have more prominent vascular relaxation impairment than aged female rats. Source of research: Bohdan Malaniak CSMC - RECOOP Young Scientists Research Grant Acknowledgements: Experimental procedures have been approved by the local Ethical Committee (Faculty of Medicine, University of Osijek) (Class:602-04/16- 08/15, No. 2158-61-07-16-143, 16.12.2016) Thank you for Cedars Sinai Medical Center’s International Research and Innovation in Medicine Program, the Association for Regional Cooperation in the Fields of Health, Science and Technology (RECOOP HST Association) for their support of our organization as participating Cedars – Sinai Medical Center - RECOOP Research Centers (CRRC).

oxidative stress ; obesity ; L-NAME ; TEMPOL ; vasorelaxation

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