Isoform profile of NOS enzyme in structure of rats’ solitary-vagal complex in arterial hypertension of various origin

Authors

  • M. V. Danukalo Zaporizhzhia State Medical University, Ukraine,
  • O. V. Hancheva Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2020.1.198141

Keywords:

nitric oxide synthase, nucleus of the solitary tract, dorsal motor nucleus, brain stem, hypertension, rats

Abstract

 

The aim of this study was to characterize the nitric oxide isoforms profile in rats’ nucleus tractus solitarii (NTS) and dorsal motor nucleus (DMN) of vagus nerve in arterial hypertension (AH) of various origin (essential (EAH) – rats of SHR line, and endocrine-salt AH).

Materials and methods. The study was performed on 30 aged male rats. Among them, 20 Wistar rats were divided into two groups – control (10 rats) and 10 rats with simulated endocrine-salt AH (ESAH) and 10 SHR rats. An immunohistochemical method was used to study the of nitric oxide synthase isoforms expression features in DMN and NTS. The following parameters were determined: the content of immunoreactive material (IRM) for the studied peptides (Uif), the relative area of the IRM (%) and the IRM concentration in 1 μm2 (Uif/μm2).

Results. It was found that in rats with both models of AH, the expression indices of all three nitric oxide synthase (NOS) isoforms in the studied structures increased. In our opinion, this is due to the activation of the studied structures in AH conditions. This must be considered as an important element of high blood pressure compensating. It is achieved through the implementation by a complex of mechanisms like reducing of the sympathetic tone and increasing of the parasympathetic tone by activating a system of secondary messengers; improving neurotrophy due to the high activity of constitutive NOS isoforms; iNOS-mediated NO overproduction, as a factor in compensating for its bioavailability in conditions of local ischemia in AH.

Conclusions. Regardless of the AH etiopathogenesis in both experimental groups, the expression of all three NOS isoforms increases in the DMN and NTS structures. In rats with EAH in the DMN and NTS structures, the expression indices of NOS isoforms have their own characteristics. So in the first structure, the largest changes in the indices of the immunoreactive material content and concentration are observed for eNOS, and the relative area for iNOS. At the same time, in the NTS structure, the largest changes in the content indices are observed for iNOS, and the concentration and relative area for eNOS. In rats with ESAH in the DMN structure, the highest changes in the indices of IRM content and concentration are observed for the endothelial isoform of NOS, and the relative area – for inducible. In the NTS structure, the IRM content changed the most for nNOS, and the concentration and relative area for iNOS.

 

References

Grassi, G., Mark, A., & Esler, M. (2015). The Sympathetic Nervous System Alterations in Human Hypertension. Circulation Research, 116(6), 976-990. https://doi.org/10.1161/circresaha.116.303604

Jamali, H. K., Waqar, F., & Gerson, M. C. (2017). Cardiac autonomic innervation. Journal of Nuclear Cardiology, 24(5), 1558-1570. https://doi.org/10.1007/s12350-016-0725-7

Wang, Y. T., & Golledge, J. (2013). Neuronal Nitric Oxide Synthase and Sympathetic Nerve Activity in Neurovascular and Metabolic Systems. Current Neurovascular Research, 10(1), 81-89. https://doi.org/10.2174/156720213804805963

Olivenza, R., Moro, M. A., Lizasoain, I., Lorenzo, P., Fernandez, A. P., Rodrigo, J., Bosca, L., & Leza, J. C. (2000). Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. Journal of Neurochemistry, 74(2), 785-791. https://doi.org/10.1046/j.1471-4159.2000.740785.x

Forstermann, U., & Sessa, W. C. (2012). Nitric oxide synthases: regulation and function. European Heart Journal, 33(7), 829-837. https://doi.org/10.1093/eurheartj/ehr304

Krowicki, Z. K., Sharkey, K. A., Serron, S. C., Nathan, N. A., & Hornby, P. J. (1997). Distribution of nitric oxide synthase in rat dorsal vagal complex and effects of microinjection of nitric oxide compounds upon gastric motor function. Journal of Comparative Neurology, 377(1), 49-69. https://doi.org/10.1002/(sici)1096-9861(19970106)377:1<49::aid-cne6>3.0.co;2-j

Dornas, W. C., & Silva, M. E. (2011). Animal models for the study of arterial hypertension. Journal of Biosciences, 36(4), 731-737. https://doi.org/10.1007/s12038-011-9097-y

Kolesnyk, Y. M., Hancheva, O. V., Abramov, A. V., Ivanenko, T. V., Tyschenko, S. V., Kuzio, N. V. (2015). Sposib modeliuvannia symptomatychnoi arterialnoi hipertenzii u dribnykh hryzuniv [Method for modeling symptomatic hypertension in rodents]. Ukraine Patent UA 102234. [in Ukrainian]. Retrieved from https://base.uipv.org/searchINV/search.php?action=viewdetails&IdClaim=217097

Kolesnyk, Y. M., Hancheva, O. V., Abramov, A. V., Kolesnyk, M. Y., Ivanenko, T. V., Tishchenko, S. V., Danukalo, M. V., & Fedotova, M. I. (2017). Sovremennye podkhody i novye metodicheskie vozmozhnosti v ocenke funkcional’nogo sostoyaniya melkikh laboratornykh zhivotnykh [Modern approaches and new methodological possibilities in the functional state of small laboratory animals assessing]. Pathologia, 14(3), 364-370. [in Russian] https://doi.org/10.14739/2310-1237.2017.3.118770

Paxinos, G. & Watson, C. (1986). The Rat Brain in Stereotaxic Coordinates. Academic Press, New York.

Kumar, G., & Rudbeck, L. (2009). Immunohistochemical staining methods. Educational Guide. 5th ed. Carpinteria, California: Dako North America.

Ferreira, T. & Rasband, W. (2012). ImageJ User Guide-IJ1.46r. Retrieved from http://imagej.nih.gov/ij/docs/guide

Zaitsev, V. M., Liflyandskii, V. G., & Marinkin, V. I. (2003). Prikladnaya meditsinskaya statistika [Applied medical statistics]. Sankt-Peterburg: Foliant. [in Russian].

Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D. A., & Stella, A. M. G. (2007). Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nature Reviews Neuroscience, 8(10), 766-775. https://doi.org/10.1038/nrn2214

Herring, N., Zaman, J. A. B., & Paterson, D. J. (2001). Natriuretic peptides like NO facilitate cardiac vagal neurotransmission and bradycardia via a cGMP pathway. American Journal of Physiology-Heart and Circulatory Physiology, 281(6), H2318-H2327.

Ogawa, H., Mizusawa, A., Kikuchi, Y., Hida, W., Miki, H., & Shirato, K. (1995). Nitric-oxide as a retrograde messenger in the nucleus-tractus-solitarii of rats during hypoxia. Journal of Physiology-London, 486(2), 495-504. https://doi.org/10.1113/jphysiol.1995.sp020828

Sy, G. Y., Bruban, V., Bousquet, P., & Feldman, J. (2001). Nitric oxide and central antihypertensive drugs - One more difference between catecholamines and imidazolines. Hypertension, 37(2), 246-249. https://doi.org/10.1161/01.hyp.37.2.246

Mollnau, H., Wendt, M., Szocs, K., Lassegue, B., Schulz, E., Oelze, M., Li, H. G., Bodenschatz, M., August, M., Kleschyov, A. L., Tsilimingas, N., Walter, U., Forstermann, U., Meinertz, T., Griendling, K., & Munzel, T. (2002). Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric Oxide/cGMP signaling. Circulation Research, 90(4), E58-E65. https://doi.org/10.1161/01.res.0000012569.55432.02

Moreira, J. D., Pernomian, L., Gomes, M. S., Moreira, R. P., do Prado, A. F., da Silva, C., & de Oliveira, A. M. (2016). Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats. European Journal of Pharmacology, 783, 11-22. https://doi.org/10.1016/j.ejphar.2016.04.050

Downloads

How to Cite

1.
Danukalo MV, Hancheva OV. Isoform profile of NOS enzyme in structure of rats’ solitary-vagal complex in arterial hypertension of various origin. Current issues in pharmacy and medicine: science and practice [Internet]. 2020Mar.10 [cited 2024Mar.29];13(1). Available from: http://pharmed.zsmu.edu.ua/article/view/198141

Issue

Section

Original research