High sucrose/fat diet and isosorbide mononitrate increase insulin resistance, nitric oxide production and myocardial apoptosis in a hypertensive rat model

Li,Ting; Bai,Bing; Tian,Chenguang; Wang,Huihui; Jiang,Deyue; Ma,Fangfei; Shan,Mengting

doi:10.3892/mmr.2018.8651

High sucrose/fat diet and isosorbide mononitrate increase insulin resistance, nitric oxide production and myocardial apoptosis in a hypertensive rat model

Authors:
- Ting Li
- Bing Bai
- Chenguang Tian
- Huihui Wang
- Deyue Jiang
- Fangfei Ma
- Mengting Shan
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Affiliations: Department of Endocrinology and Metabolic Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China, Department of Endocrinology and Metabolic Diseases, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Henan Polytechnic University, Jiaozuo, Henan 454000, P.R. China
Published online on: February 28, 2018 https://doi.org/10.3892/mmr.2018.8651
Pages: 6789-6795

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Abstract

The present study aimed to investigate the association between insulin resistance (IR), nitric oxide (NO) production and myocardial apoptosis in a background of coexisting hypertension in a rodent animal model. A hypertensive rat model was established by feeding Wistar and spontaneously hypertensive rats (SHR) with a high sucrose/fat (HSF) diet for 12 weeks, in conjunction with isosorbide mononitrate (ISMN). Increased IR, NO content, apoptotic gene and protein expression, and morphological alterations within rat myocardium were evaluated. Following a total of 12 weeks of feeding with HSF and ISMN resulted in increased IR and NO content within the myocardial tissue of Wistar and SHR rats. HSF and ISMN activated myocardial apoptosis by downregulating the gene transcription and protein expression levels of the anti‑apoptotic B‑cell lymphoma 2 (Bcl‑2), and increasing the pro‑apoptotic Bcl‑2 associated X protein. Apoptosis was demonstrated by DNA fragmentation in terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling assay. In all experiments, the combination of HSF and ISMN was associated with more pronounced effects, indicating the possible synergistic effects. In addition, the correlation analysis in the Wistar rats fed with HSF only, revealed a positive association between NO production and IR. The results of the present study indicated that HSF and ISMN simultaneously increased IR, NO production and myocardial apoptosis in the hypertensive rat model, and may therefore contribute to investigations into the long‑term clinical use of ISMN in hypertensive patients.

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