The features of the nitric oxide system in the left ventricle myocardium in the rats with experimental intermittent hypoxia of different duration

Authors

  • Yu. M. Kolesnyk Zaporizhzhia State Medical University, Ukraine,
  • M. I. Isachenko Zaporizhzhia State Medical University, Ukraine,
  • O. V. Melnikova Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1237.2019.3.188783

Keywords:

nitric oxide synthase, NOS isoforms, left ventricle, heart, intermittent hypoxia, rats, Wistar

Abstract

 

The aim was to determine the features of the NO system status in the left ventricular myocardium in the rats with intermittent hypoxic hypobaric hypoxia during 15 and 60 days.

Material and methods. The study was conducted on the 30 Wistar male rats, which were divided into 3 experimental groups: the 1st – control, the 2nd – rats exposed to intermittent hypoxia during 15 days and the 3rd group – the rats exposed to intermittent hypoxia during 60 days. Blood pressure was measured in all the rats. The objects and methods of the study were blood plasma (nitrotyrosine detection with immunoassay) and the myocardium of the left ventricle (concentration of nitrites by Griess nitrite test and content of immunoreactive material to the nitric oxide synthase isoforms by immunofluorescence method). mRNA expression of NOS isoforms was determined by PCR-RT method in the myocardium.

Results. In the rats with 15-day hypoxia there was an increase in systolic pressure compared to control, and in 60-day hypoxia, there was also an increase in diastolic pressure although this changes were within the normotensive range. mRNA to all the myocardial NOS isoforms was characterized by an increase in both hypoxia groups. At the same time, the indices of the immunoreactive material content to the NOS isoforms were dependent on the hypoxia term. The concentration of the nitrotyrosine increased in both hypoxic groups, but in the long term it occurred along with a decrease in the level of nitrite, which indicates the possibility of nitro-oxidative stress.

Conclusions. The 15-day intermittent hypoxia changes the myocardial NO system: an increase in the expression of all 3 isoforms, an increase in the nitrite and the nitrotyrosine content. iNOS becomes the predominant form of the enzyme in the myocardium with the increasing its mRNA. In 60-day hypoxia, the profile of the NOS enzyme is characterized by increased expression of the constitutive isoforms and decreased inducible NOS expression that was accompanied with significant increase in mRNA of all three forms. The level of terminal metabolites of NO was characterized by a decrease in the nitrite while the content of the nitrotyrosine increased.

 

References

De Haas, S., Ghossein-Doha, C., Geerts, L., van Kuijk, S. M. J., van Drongelen, J., & Spaanderman, M. E. A. (2017). Cardiac remodeling in normotensive pregnancy and in pregnancy complicated by hypertension: Systematic review and meta-analysis. Ultrasound in Obstetrics and Gynecology, 50(6), 683-696. https://doi.org/10.1002/uog.17410

Yalçin, F., Kucukler, N., Cingolani, O., Mbiyangandu, B., Sorensen, L., Pinherio, A., . . . Abraham, T. P. (2019). Evolution of ventricular hypertrophy and myocardial mechanics in physiological and pathological hypertrophy. Journal of Applied Physiology, 126(2), 354-362. https://doi.org/10.1152/japplphysiol.00199.2016

Haque, Z. K., & Wang, D. (2017). How cardiomyocytes sense pathophysiological stresses for cardiac remodeling. Cellular and Molecular Life Sciences, 74(6), 983-1000. https://doi.org/10.1007/s00018-016-2373-0

Manukhina, E. B., Downey, H. F., & Mallet, R. T. (2006). Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia. Experimental Biology and Medicine, 231(4), 343-365. https://doi.org/10.1177/153537020623100401

Treuer, A. V., & Gonzalez, D. R. (2015). Nitric oxide synthases, S-nitrosylation and cardiovascular health: From molecular mechanisms to therapeutic opportunities (review). Molecular Medicine Reports, 11(3), 1555-1565. https://doi.org/10.3892/mmr.2014.2968

Manukhina, E. B., Downey, H. F., Mallet, R. T., Malyshev, I. Yu., & Vanin, A. F. (2012). Depo oksida azota (NO) i ego adaptivnaya rol' v serdechno-sosudistoi sisteme. [Nitric oxide (NO) stores and their adaptive function in the cardiovascular system]. Patogenez, 10(2), 19-27. [in Russian].

Abe, H., Semba, H., & Takeda, N. (2017). The Roles of Hypoxia Signaling in the Pathogenesis of Cardiovascular Diseases. Journal of Atherosclerosis and Thrombosis, 24(9), 884-894. https://doi.org/10.5551/jat.RV17009

Kolesnyk, Y. M., Isachenko, M. I., Melnikova, O. V., & Hrekova, T. A. (2018). Characteristics of the nitric oxide system indicators in the left ventricle myocardium in SHR. Pathologia(3), 278-283. https://doi.org/10.14739/2310-1237.2018.3.151670

Kolesnyk, Y. M., Hancheva, O. V., Abramov, A. V., Ivanenko, T. V., Fedotova, M. I., & Danukalo, M. V. (2016). Sposib modeliuvannia fiziolohichnoho remodeliuvannia miokarda u dribnykh hryzuniv [Method for modeling physiological myocardial remodeling in small rodents]. Ukraine Patent UA 112290. Retrieved from https://base.uipv.org/searchINV/search.php?action=viewdetails&IdClaim=230277

Pro zakhyst tvaryn vid zhorstokoho povodzhennia. Zakon Ukrainy vid 21.02.2006 no 3447-IV [On the Protection of Animals from Brutal Treatment. Law of Ukraine on February 21, 2006 no 3447-IV] Retrieved from https://zakon.rada.gov.ua/laws/main/3447-IV

Gorbunov, N. V. (1995). Opredelenie stabil'nykh metabolitov oksida azota po Grissu v biologicheskom material [Determination of stable nitric oxide metabolites by Griss in biological material]. Byulleten' ehksperimental'noi biologii i meditsiny, 120(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 [Peculiarities of expression of nitric oxide synthase isoforms in left ventricular myocardium of rats in arterial hypertension of various geneses]. Aktualni problemy suchasnoi medytsyny, 17(4.2), 91-95. [in Ukrainian].

Zaitsev, V. M., Liflyandskii, V. G., & Marinkin, V. I. (2006). Prikladnaya meditsinskaya statistika. [Applied Medical Statistics]. St. Petersburg: Foliant [in Russian].

Chis, I. C., Baltaru, D., Dumitrovici, A., Coseriu, A., Radu, B. C., Moldovan, R., & Muresan, A. (2018). Protective effects of quercetin from oxidative/nitrosative stress under intermittent hypobaric hypoxia exposure in the rat's heart. Physiology International, 105(3), 233-246. https://doi.org/10.1556/2060.105.2018.3.23

Na, H., Chung, H., Ha, K., Lee, H., Kwon, Y., Billiar, T. R., & Kim, Y. (2008). Chapter 17 detection and measurement for the modification and inactivation of caspase by nitrosative stress in vitro and in vivo. https://doi.org/10.1016/S0076-6879(08)01217-2

Rossier, B. C., Bochud, M., & Devuyst, O. (2017). The hypertension pandemic: An evolutionary perspective. Physiology, 32(2), 112-125. https://doi.org/10.1152/physiol.00026.2016

Meerson, F. Z., & Pshennikova, M. G. (1988). Adaptatsiya k stressovym situatsiyam i fizicheskim nagruzkam [Adaptation to stressful situations and physical activity]. Moscow: Izdatelstvo Meditsina. [in Russian].

Zhang, Y. H. (2017). Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress. F1000Research, 6 https://doi.org/10.12688/f1000research.10128.1

Carnicer, R., Suffredini, S., Liu, X., Reilly, S., Simon, J. N., Surdo, N. C., . . . Casadei, B. (2017). The subcellular localization of neuronal nitric oxide synthase determines the downstream effects of NO on myocardial function. Cardiovascular Research, 113(3), 321-331. https://doi.org/10.1093/cvr/cvx002

Lefer, D. J. (2006). Induction of HIF-1α and iNOS with siRNA: A novel mechanism for myocardial protection. Circulation Research, 98(1), 10-11. https://doi.org/10.1161/01.RES.0000200398.52220.cc

Ding, H., Zhu, H., Dong, J., Zhu, W., Yang, W., Yang, H. & Zhou, Z. (2005). Inducible nitric oxide synthase contributes to intermittent hypoxia against ischemia/reperfusion injury. Acta Pharmacologica Sinica, 26(3), 315-322. https://doi.org/10.1111/j.1745-7254.2005.00046.x

La Padula, P. H., Etchegoyen, M., Czerniczyniec, A., Piotrkowski, B., Arnaiz, S. L., Milei, J., & Costa, L. E. (2018). Cardioprotection after acute exposure to simulated high altitude in rats. role of nitric oxide. Nitric Oxide - Biology and Chemistry, 73, 52-59. https://doi.org/10.1016/j.niox.2017.12.007

Capettini, L. S. A., Cortes, S. F., & Lemos, V. S. (2010). Relative contribution of eNOS and nNOS to endothelium-dependent vasodilation in the mouse aorta. European Journal of Pharmacology, 643(2-3), 260-266. https://doi.org/10.1016/j.ejphar.2010.06.066

Forstermann, U., & Munzel, T. (2006). Endothelial nitric oxide synthase in vascular disease - From marvel to menace. Circulation, 113(13), 1708-1714. https://doi.org/10.1161/circulationaha.105.602532

Macdonald, W. A., & Hool, L. C. (2008). The effect of acute hypoxia on excitability in the heart and the L-type calcium channel as a therapeutic target. Current Drug Discovery Technologies, 5(4), 302-311. https://doi.org/10.2174/157016308786733546

Wyatt, A. W., Steinert, J. R., & Mann, G. E. (2004). Modulation of the L-arginine/nitric oxide signalling pathway in vascular endothelial cells https://doi.org/10.1042/bss0710143

Rus, A., del Moral, M., Molina, F., & Peinado, M. (2011). Does inducible NOS have a protective role against hypoxia / reoxygenation injury in rat heart? Cardiovascular Pathology, 20(1), e17-e25. https://doi.org/10.1016/j.carpath.2010.01.002

Downloads

How to Cite

1.
Kolesnyk YM, Isachenko MI, Melnikova OV. The features of the nitric oxide system in the left ventricle myocardium in the rats with experimental intermittent hypoxia of different duration. Pathologia [Internet]. 2019Dec.23 [cited 2024Mar.28];(3). Available from: http://pat.zsmu.edu.ua/article/view/188783

Issue

Section

Original research