The influence of the perinatal chronic hyperglycaemia on the pattern of NOS isoforms expression in left ventricle myocardium in male rats of pre-pubertal age

Authors

  • O. V. Gancheva Zaporizhzhia State Medical University,
  • Yu. M. Kolesnyk Zaporizhzhia State Medical University,
  • Yu. I. Vorodeeva Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2310-1237.2016.3.86938

Keywords:

Nitric Oxide Synthase, Gestational Diabetes, Expression Gene

Abstract

The aim of our study was to find out the features of the nitric oxide synthase (NOS) isoforms expression in longitudinal and transversal layers of the myocardium of the left ventricle in male rats of 3 months, which are descendants of female rats with experimental gestational diabetes (EGD).

Materials and methods. Study was carried out on 10 male rats descendants of female rats with normal course of pregnancy and 10 descendants of female rats with EGD. We evaluated the expression of neuronal, endothelial and inducible isoforms of NOS in histological sections both of transversal and longitudinal layers of the myocardium of left ventricle. With the aim to analyze the pattern of the NOS isoforms expression in 5 um histological slices of left ventricle myocardium we have carried out a complex of histochemical assays. Slices were allocated to 3 groups: 1st one was incubated with rabbit IgG to neuronal NOS (Santa Cruz Biotechnology, USA) in dilution of 1:200; 2nd group underwent the incubation with rabbit IgG to endothelial NOS (eNos) (Santa Cruz Biotechnology, USA) in dilution 1:200; 3rd group was incubated with mice IgG to inducible NOS (iNos) conjugated with FITC (Santa Cruz Biotechnology, USA) in dilution of 1:200. The analysis of images was carried out with VIDAS-2.5 application package (Kontron Elektronik, Germany). Microimages of the left ventricle myocardium obtained with AxioScope (Carl Zeiss, Germany) and COHU 4922 (COHU Inc., USA) camera were processed in the system of digital image analysis VIDAS-386 (Kontron Elektronik, Germany).

Results. In the study we have found that prenatal hyperglycaemia leads to the significant changes of the expression of NOS isoforms in the myocardium of left ventricle in male rats descendants of females with EGD, and the contain and the allocation of these enzymes are dependent both on type of the enzyme and its location in muscular layers. For eNOS the increase of the expression and the allocation in both transversal and longitudinal layers was typical, and for nNOS and iNOS we have found the significant decrease of the expression in transversal layers and the significant increase in longitudinal layers.

Conclusion.We believe, the glucose homeostasis violation in foetus during the last trimester of the pregnancy changes the ratio of the NOS isoforms expression in the left ventricle myocardium and affects the balance of them in different layers, which could be a reason of the cardiovascular pathology development in adulthood. 

References

Paslawska, U., Kiczak, L., Bania, J., Paslawski, R., Janiszewski, A., Dzięgiel, P. et al. (2016). Inducible NO synthase is constitutively expressed in porcine myocardium and its level decreases along with tachycardia-induced heart failure. Cardiovascular Pathology, 25(1), 3–11. doi: 10.1016/j.carpath.2015.08.003.

Smiljić, S., Nestorović, V., & Savić, S. (2014). Modulatory role of nitric oxide in cardiac performance. Med Pregl., 67(9–10), 345–52.

Ito, Y., Ohkubo, T., Asano, Y., Hattori, K., Shimazu, T., Yamazato, M. et al. (2010). Nitric Oxide Production during Cerebral Ischemia and Reperfusion in eNOS- and nNOS-Knockout Mice. CNR, 7(1), 23–31.

Tan, W., Xue-bin, C., Tian, Z., Xiao-wu, C., Pei-pei, H., Zhi-bin, C., & Bei-sha, T. (2016). Effects of simvastatin on the expression of inducible nitric oxide synthase and brain-derived neurotrophic factor in a lipopolysaccharide-induced rat model of Parkinson disease. International Journal Of Neuroscience, 126(3), 278–286. doi: 10.3109/00207454.2015.1012758.

Aliev, G., Palacios, H., Gasimov, E., Obrenovich, M., Morales, L., Leszek, J. et al. (2010). Oxidative Stress Induced Mitochondrial Failure and Vascular Hypoperfusion as a Key Initiator for the Development of Alzheimer Disease. Pharmaceuticals, 3(1), 158–187. doi: 10.3390/ph3010158.

Correia-Costa, L., Sousa, T., Morato, M., Cosme, D., Afonso, J., Areias, J. et al. (2016). Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function. British Journal Of Nutrition, 116(05), 805–815. doi: 10.1017/S0007114516002804.

Tran, C., Fox, M., Vallance, P., & Leiper, J. (2000). Chromosomal Localization, Gene Structure, and Expression Pattern of DDAH1: Comparison with DDAH2 and Implications for Evolutionary Origins. Genomics, 68(1), 101–105. doi: 10.1006/geno.2000.6262.

Gancheva, O., Melnikova, O., Vorodeeva, Y., et al. (2012). Osobennosti variabel´nosti serdechnogo ritma u krys prepubertatnogo vozrasta, perenesshykh vnutriutnrobnuyu giperglikemiyu [Features of the heart rate variability in rats of pubertal age, which were undergone intrauterine hyperglycaemia]. Klinichna ta eksperymentalna patolohiia, 9, 3(41), 30–32. [in Ukrainian].

Kolesnyk, Y., Belienichev, I., Abramov, A., Hancheva, O., Kamyshnyi, O., & Hrekova, T. (patentee) (2006). Pat. 17281 Ukraina, MPK G09 №23/28. Sposib modeliuvannia hestatsiinoho diabetu u shchuriv linii Vistar dlia vyvchennia yoho naslidkiv dlia nashchadkiv [Patent 17281 of Ukraine MPK G09 №23/28. Method of the modelling of gestational diabets in Wistar rats with aim to study its consequences in descendants]. Biuleten, 9. [in Ukrainian].

Bens, S., Kolarova, J., Beygo, J., Buiting, K., Caliebe, A., Eggermann, T. et al. (2016). Phenotypic spectrum and extent of DNA methylation defects associated with multilocus imprinting disturbances. Epigenomics, 8(6), 801–816. doi: 10.2217/epi-2016-0007.

Yan, J. & Yang, H. (2013). Gestational diabetes mellitus, programing and epigenetics. The Journal Of Maternal-Fetal & Neonatal Medicine, 27(12), 1266–1269. doi: 10.3109/14767058.2013.853733.

Gluckman, P., & Hanson, M. A. (2004). Living with the Past: Evolution, Development, and Patterns of Disease. Science, 305(5691), 1733–1736. doi: 10.1126/science.1095292.

Varadinova, M., Metodieva, R., & Boyadzhieva, N. (2015). Fetal programming of metabolic disorders. Akush Ginekol (Sofiia), 54(8), 32–36.

Crudo, A., Petropoulos, S., Moisiadis, V., Iqbal, M., Kostaki, A., Machnes, Z. et al. (2012). Prenatal Synthetic Glucocorticoid Treatment Changes DNA Methylation States in Male Organ Systems: Multigenerational Effects. Endocrinology, 153(7), 3269–3283. http://dx.doi.org/10.1210/en.2011-2160. doi: 10.1210/en.2011-2160.

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1.
Gancheva OV, Kolesnyk YM, Vorodeeva YI. The influence of the perinatal chronic hyperglycaemia on the pattern of NOS isoforms expression in left ventricle myocardium in male rats of pre-pubertal age. Pathologia [Internet]. 2016Dec.23 [cited 2024Jul.8];(3). Available from: http://pat.zsmu.edu.ua/article/view/86938

Issue

No. 3 (2016)

Section

Original research

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