Pathogenetic features of the nitric oxide system state in the left ventricular myocardium of the rats with experimental arterial hypertension
DOI:
https://doi.org/10.12775/JEHS.2020.10.08.058Keywords
nitric oxide synthase, NOS isoforms, myocardium, left ventricle, heart, Wistar rats, endocrine-salt arterial hypertension, secondary hypertension.Abstract
The aim was to determine the pathogenetic features of the NO system in the myocardium of the left ventricle in the rats with endocrine-salt hypertension.Material and methods. The experiment was conducted on 20 male rats 220-290 g weight, 6–10 months old which were divided into 2 experimental groups: 1st – the control group (10 intact normotensive male Wistar rats); 2nd – 10 male Wistar rats with endocrine-salt arterial hypertension. Systolic and diastolic BP levels were measured in all the rats using a system of non-invasive arterial pressure measurement BP-2000. The objects of study in the experimental animals were blood plasma in which the nitrotyrosine level was measured, and the fragment of left ventricle, which was divided into two parts, one of which was homogenized using a Silent Crusher S homogenizer (Heidolph, Germany), in which nitrites level was determined. Concentration of immunoreactive material to NOS isoforms was detected with immunofluorescence method. The study of NOS mRNA isoforms expression in the left ventricular myocardium homogenates was carried out using a real-time polymerase chain reaction
Results. In the experiment, an increase in all 3 isoforms and their mRNA was obtained. In the study, a decrease in nitrites concentration and a significant increase in nitrotyrosine levels, indicates the development of nitroso-oxidative stress.
Conclusions. The development of experimental endocrine-salt hypertension in the Wistar rats leads to a stable increase in mean blood pressure by 65 % compared to control. Endocrine-salt arterial hypertension in Wistar rats is characterized by an increased mRNA content of all three isoforms of nNOS, eNOS and iNOS by 2.7, 2.8 and 5.7 times, respectively, compared to the control; increased expression of immunoreactive material to isoforms in transverse fibers by 14.3 %, 16.2 % and 18.5 %, respectively; in longitudinal fibers IRM to nNOS was higher by 8.3 %, to iNOS - by 8. 5%, but to eNOS it was lower by 7.6 %. At the same time, nitrites level decreased by 11.7 % and nitrotyrosine concentration was significantly higher, exceeding the control value by 88.5 %.
References
Charles, L., Triscott, J., & Dobbs, B. (2017). Secondary Hypertension: Discovering the Underlying Cause. American family physician, 96(7), 453–461.
Funder J. W. (2017). Aldosterone and Mineralocorticoid Receptors-Physiology and Pathophysiology. International journal of molecular sciences, 18(5), 1032. https://doi.org/10.3390/ijms18051032.
Fjeld, C. C., Birdsong, W. T., & Goodman, R. H. (2003). Differential binding of NAD+ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor. Proceedings of the National Academy of Sciences of the United States of America, 100(16), 9202–9207. https://doi.org/10.1073/pnas.1633591100.
Chai, W., Garrelds, I. M., Arulmani, U., Schoemaker, R. G., Lamers, J. M., & Danser, A. H. (2005). Genomic and nongenomic effects of aldosterone in the rat heart: why is spironolactone cardioprotective?. British journal of pharmacology, 145(5), 664–671. https://doi.org/10.1038/sj.bjp.0706220.
Imunohistokhimichna i morfo-densytometrychna diahnostyka patolohichnoho remodeliuvannia miokardu pry arterialnii hipertenzii ta tsukrovomu diabeti : Metodychni rekomendatsii / M-vo okhorony zdorovia Ukrainy, Ukrmedpatentinform MOZU ; uklad. Yu. M. Kolesnyk [ta in.]. - K. : B.v., 2015. - 24 s. : rys. - Byblyohr.: s. 22-23 [in Ukrainian].
Tomaschitz, A., Pilz, S., Ritz, E., Obermayer-Pietsch, B., & Pieber, T. R. (2010). Aldosterone and arterial hypertension. Nature reviews. Endocrinology, 6(2), 83–93. https://doi.org/10.1038/nrendo.2009.263.
Vassiliadi, D., & Tsagarakis, S. (2017). Cardiac hypertrophy in Cushing’s syndrome: if not hypertension then what?. Endocrine, 56(3), 453-455. doi: 10.1007/s12020-017-1260-2.
De, P., Roy, S. G., Kar, D., & Bandyopadhyay, A. (2011). Excess of glucocorticoid induces myocardial remodeling and alteration of calcium signaling in cardiomyocytes. The Journal of endocrinology, 209(1), 105–114. https://doi.org/10.1530/JOE-10-0431.
Iwashima, F., Yoshimoto, T., Minami, I., Sakurada, M., Hirono, Y., & Hirata, Y. (2008). Aldosterone induces superoxide generation via Rac1 activation in endothelial cells. Endocrinology, 149(3), 1009–1014. https://doi.org/10.1210/en.2007-0864.
Nediani, C., Borchi, E., Giordano, C., Baruzzo, S., Ponziani, V., Sebastiani, M., Nassi, P., Mugelli, A., d'Amati, G., & Cerbai, E. (2007). NADPH oxidase-dependent redox signaling in human heart failure: relationship between the left and right ventricle. Journal of molecular and cellular cardiology, 42(4), 826–834. https://doi.org/10.1016/j.yjmcc.2007.01.009.
Iyer, A., & Brown, L. (2009). Is mycophenolate more than just an immunosuppressant?-An overview. Indian journal of biochemistry & biophysics, 46(1), 25–30.
Li, J. M., & Shah, A. M. (2004). Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology. American journal of physiology. Regulatory, integrative and comparative physiology, 287(5), R1014–R1030. https://doi.org/10.1152/ajpregu.00124.2004.
Cruz-Topete, D., Oakley, R., & Cidlowski, J. (2020). Glucocorticoid Signaling and the Aging Heart. Frontiers In Endocrinology, 11. doi: 10.3389/fendo.2020.00347.
Fenning, A., Harrison, G., Rose'meyer, R., Hoey, A., & Brown, L. (2005). l-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats. American journal of physiology. Heart and circulatory physiology, 289(4), H1408–H1416. https://doi.org/10.1152/ajpheart.00140.2005.
Kolesnyk, Yu & Isachenko, Mariia & Melnikova, Olga. (2019). The features of the nitric oxide system in the left ventricle myocardium in the rats with experimental intermittent hypoxia of different duration. Pathologia. 16(3), 308–314. doi: 10.14739/2310-1237.2019.3.188783.
Fedotova, M., & Kolesnyk, Y. (2018). P89Comparative analysis of the status of the nitric oxide system in the left ventricle of heart in rats with experimental hypertension of different origin. Cardiovascular Research, 114(suppl_1), S23-S24. doi: 10.1093/cvr/cvy060.053.
Pat. 102234 Ukraina, MPK G09V 23/28. Sposib modeliuvannia symptomatychnoi arterialnoi hipertenzii u dribnykh hryzuniv / Kolesnyk Yu. M., Hancheva O. V., Abramov A. V., Ivanenko T. V.; Tishchenko S.V., Kuzo N. V. zaiavnyk ta patentovlasnyk ZDMU. – № u 2015 03152; zaiavl. 06.04.15 ; opubl. 26.10.15, Biul. № 20 [in Ukrainian].
Zakon Ukrainy № 3447-IV «Pro zakhyst tvaryn vid zhorstkoho povodzhennia» / Vidomosti Verkhovnoi Rady Ukrainy. – 2006. – № 27. – s230 [in Ukrainian].
Horbunov N.V. (1995) Opredelenye stabylnikh metabolytov oksyda azota po Hryssu v byolohycheskom materyale. Biulleten эksperymentalnoi byolohyy y medytsynы, 7, 40–48 [in Russian].
Fedotova M.I., Kovalov M.M.., Zhulinskyi V.O., Kadzharian Ye.V. (2017) Osoblyvosti ekspresii izoform syntazy oksydu azotu u miokardi livoho shlunochka shchuriv pry arterialnii hipertenzii riznoho henezu. Aktualni problemy suchasnoi medytsyny: Visnyk Ukrainskoi medychnoi stomatolohichnoi akademii, 17,4(60), 91−95 [in Ukrainian].
Yu. M. Kolesnyk, M. I. Isachenko, O. V. Melnikova, T. A. Hrekova (2018). Characteristics of the nitric oxide system indicators in the left ventricle myocardium in SHR. Patolohiia, T. 15, № 3(44), 278–283. doi: 10.14739/2310-1237. 2018.3.151670.
Zaitsev, V. M., & Marynkyn, V. Y. (2006). Prykladnaia medytsynskaia statystyka [in Russian].
Danukalo M. V., Hancheva O. V. (2020). Isoform profile of NOS enzyme in structure of rats’ solitary-vagal complex in arterial hypertension of various origin. Актуальні питання фармацевтичної і медичної науки та практики, Т. 13, №1(32), 78-83. doi: 10.14739/2409-2932.2020.1.198141.
Ignarro L. J. (2019). Nitric oxide is not just blowing in the wind. British journal of pharmacology, 176(2), 131–134. https://doi.org/10.1111/bph.14540
Ritchie, R. H., Drummond, G. R., Sobey, C. G., De Silva, T. M., & Kemp-Harper, B. K. (2017). The opposing roles of NO and oxidative stress in cardiovascular disease. Pharmacological research, 116, 57–69. https://doi.org/10.1016/j.phrs.2016.12.017
Zhang Y. H. (2016). Neuronal nitric oxide synthase in hypertension - an update. Clinical hypertension, 22, 20. https://doi.org/10.1186/s40885-016-0055-8
Zhang, Y., Jin, C., Jang, J., & Wang, Y. (2014). Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology. The Journal Of Physiology, 592(15), 3189-3200. doi: 10.1113/jphysiol.2013.270306.
Farah, C., Michel, L., & Balligand, J. L. (2018). Nitric oxide signalling in cardiovascular health and disease. Nature reviews. Cardiology, 15(5), 292–316. https://doi.org/10.1038/nrcardio.2017.224
Zhu, J., Song, W., Xu, S., Ma, Y., Wei, B., Wang, H., & Hua, S. (2020). Shenfu Injection Promotes Vasodilation by Enhancing eNOS Activity Through the PI3K/Akt Signaling Pathway In Vitro. Frontiers in pharmacology, 11, 121. https://doi.org/10.3389/fphar.2020.00121
Paton, J. F., Kasparov, S., & Paterson, D. J. (2002). Nitric oxide and autonomic control of heart rate: a question of specificity. Trends in neurosciences, 25(12), 626–631. https://doi.org/10.1016/s0166-2236(02)02261-0
Zhang Y. H. (2017). Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress. F1000Research, 6, 742. https://doi.org/10.12688/f1000research.10128.1.
Ye, F., He, J., Wu, X., Xie, J., Chen, H., Tang, X., Lai, Z., Huang, R., & Huang, J. (2019). The regulatory mechanisms of Yulangsan MHBFC reversing cardiac remodeling in rats based on eNOS-NO signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 117, 109141. https://doi.org/10.1016/j.biopha.2019.109141
Yu, X., Ge, L., Niu, L., Lian, X., Ma, H., & Pang, L. (2018). The Dual Role of Inducible Nitric Oxide Synthase in Myocardial Ischemia/Reperfusion Injury: Friend or Foe?. Oxidative medicine and cellular longevity, 2018, 8364848. https://doi.org/10.1155/2018/8364848.
Cuzzocrea, S., Ayroldi, E., Di Paola, R., Agostini, M., Mazzon, E., & Bruscoli, S. et al. (2005). Role of glucocorticoid-induced TNF receptor family gene (GITR) in collagen-induced arthritis. The FASEB Journal, 19(10), 1253-1265. doi: 10.1096/fj.04-3556com
Puzserova, A., & Bernatova, I. (2016). Blood pressure regulation in stress: focus on nitric oxide-dependent mechanisms. Physiological research, 65(Suppl 3), S309–S342. https://doi.org/10.33549/physiolres.933442.
Tejero, J., Shiva, S., & Gladwin, M. T. (2019). Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation. Physiological reviews, 99(1), 311–379. https://doi.org/10.1152/physrev.00036.2017.
Downloads
Published
How to Cite
Issue
Section
License
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 559
Number of citations: 0