The role of neuronal NO synthase in the respiratory effects of the proinflammatory cytokine TNF-α
DOI:
https://doi.org/10.33910/2687-1270-2021-2-2-157-164Keywords:
cytokines, TNF-α, hypoxia, chemoreflex, respiration, ventilation, neuronal nitric oxide synthaseAbstract
In our previous studies we showed that an increase in the systemic or cerebral level of proinflammatory cytokines has a modulating effect on the reflex control of respiration. The aim of this study was to investigate the possible involvement of neuronal nitric oxide synthase (nNOS) in the hypoxic ventilatory response induced by an increased systemic level of the proinflammatory cytokine Tumor necrosis factor — α (TNF-α). To achieve this goal, we conducted experiments on urethane anesthetized rats with intravenous administration of TNF-α before and after pretreatment with 7-nitroindazole specific inhibitor of nNOS. The hypoxic ventilation response was assessed by rebreathing with a hypoxic gas mixture before and after administration of TNF-α. We found that TNF-α increased the lung ventilation in normoxia but decreased the ventilatory response to hypoxia. Pretreatment with nNOS inhibitor reduced respiratory effects of TNF-α. We believe that TNF-α can participate in the modulation of peripheral hypoxic chemoreflex not only in pathological, but also in normal physiological conditions through the activation of constitutive nNOS in the glomus cells of the carotid bodies. This makes the respiratory system urgently respond to an increase in the level of pro-inflammatory cytokines in the circulatory system. The obtained data made it possible to improve the understanding of how systemic inflammation affects the respiratory function.
References
Aleksandrov, V. G., Aleksandrova, N. P., Tumanova, T. S. et al. (2015) Uchastie NO-ergicheskikh mekhanizmov v realizatsii respiratornykh effektov provospalitel’nogo tsitokina interlejkina-1-beta [Participation of NO-ergic mechanisms in realization of respiratory effects of pro-inflammatory cytokine interleukin-1-beta]. Rossijskij fiziologicheskij zhurnal im. I. M. Sechenova — Russian Journal of Physiology, vol. 101, no. 12, pp. 1372–1384. (In Russian)
Aleksandrova, N. P., Danilova, G. A., Aleksandrov, V. G. (2015) Cyclooxygenase pathway in modulation of the ventilatory response to hypercapnia by interleukin-1β in rats. Respiratory Physiology and Neurobiology, vol. 209, pp. 85–90. https://www.doi.org/10.1016/j.resp.2014.12.006 (In English)
Aleksandrova, N. P., Danilova, G. A., Aleksandrov, V. G. (2017) Interleukin-1beta suppresses the ventilatory hypoxic response in rats via prostaglandin-dependent pathways. Canadian Journal of Physiology and Pharmacology, vol. 95, no. 6, pp. 681–685. https://www.doi.org/10.1139/cjpp-2016-0419 (In English)
Aleksandrova, N. P., Klinnikova, A. A., Danilova, G. A. (2020) Cyclooxygenase and nitric oxide synthase pathways mediate the respiratory effects of TNF-α in rats. Respiratory Physiology and Neurobiology, vol. 284, article 103567. https://www.doi.org/10.1016/j.resp.2020.103567 (In English)
Brenman, J. E., Bredt, D. S. (1996) Nitric oxide signaling in the nervous system. Methods in Enzymology, vol. 269, pp. 119–129. (In English)
Gauda, E. B., Shirahata, M., Masona, A. et al. (2013) Inflammation in the carotid body during development and its contribution to apnea of prematurity. Respiratory Physiology and Neurobiology, vol. 185, no. 1, pp. 120–131. https://www.doi.org/10.1016/j.resp.2012.08.005 (In English)
Graff, G. R., Gozal, D. (1999) Cardiorespiratory responses to interleukin-1beta in adult rats: Role of nitric oxide, eicosanoids and glucocorticoids. Archive of Physiology and Biochemistry, vol. 107, no. 2, pp. 97–112. https://www.doi.org/10.1076/apab.107.2.97.4344 (In English)
Herlenius, E. (2011) An inflammatory pathway to apnea and autonomic dysregulation. Respiratory Physiology and Neurobiology, vol. 178, no. 3, pp. 449–457. https://www.doi.org/10.1016/j.resp.2011.06.026 (In English)
Höhler, B., Mayer, B., Kummer, W. (1994) Nitric oxide synthase in the rat carotid body and carotid sinus. Cell Tissue Research, vol. 276, no. 3, pp. 559–564. https://www.doi.org/10.1007/BF00343953 (In English)
Iturriaga, R. (2001) Nitric oxide and carotid body chemoreception. Biological Research, vol. 34, no. 2, pp. 135–139. https://www.doi.org/10.4067/s0716-97602001000200019 (In English)
Klinnikova, A. (2018) The effect of pro-inflammatory cytokine TNF–α on lung ventilation and hypoxic chemoreception. Pathophysiology, vol. 25, no. 3, p. 228. https://www.doi.org/10.1016/j.pathophys.2018.07.146 (In English)
Lam, S.-Y., Tipoe, G. L., Liong, E. C., Fung, M.-L. (2008) Chronic hypoxia upregulates the expression and function of proinflammatory cytokines in the rat carotid body. Histochemistry and Cell Biology, vol. 130, no. 3, pp. 549–559. https://www.doi.org/10.1007/s00418-008-0437-4 (In English)
Li, Y.-L., Li, Y.-F., Liu, D. et al. (2005) Gene transfer of neuronal nitric oxide synthase to carotid body reverses enhanced chemoreceptor function in heart failure rabbits. Circulation Research, vol. 97, no. 3, pp. 260–267. https://www.doi.org/10.1161/01.res.0000175722.21555.55 (In English)
Moya, E. A., Alcayaga, J., Iturriaga, R. (2012) NO modulation of carotid body chemoreception in health and disease. Respiratory Physiology and Neurobiology, vol. 184, no. 2, pp. 158–164. https://www.doi.org/10.1016/j.resp.2012.03.019 (In English)
Nakamori, T., Morimoto, A., Murakami, N. (1993) Effect of a central CRF antagonist on cardiovascular and thermoregulatory responses induced by stress or IL-1β. American Journal of Physiology — Regulatory, Integrative and Comparative Physiology, vol. 265, no. 4, pp. R834–R839. https://www.doi.org/10.1152/ajpregu.1993.265.4.R834 (In English)
Sitdikova, G. F., Yakovlеv, A. V., Zefirov, A. L. (2014) Gazomediatory: ot toksicheskikh effektov k regulyatsii kletochnikh funktsii i ispol’zovaniyu v klinike [Gas mediators: From toxic effects to the regulation of cellular functions and clinical application]. Byulleten’ sibirskoj meditsiny — Bulletin of Siberian Medicine, vol. 13, no. 6, pp. 185–200. (In Russian)
Tanaka, K., Chiba, T. (1994) Nitric oxide synthase containing neurons in the carotid body and sinus of the guinea pig. Microscopy Research and Technique Journal, vol. 29, no. 2, pp. 90–93. https://www.doi.org/10.1002/jemt.1070290205 (In English)
Valdés, V., Mosqueira, M., Rey, S. et al. (2003) Inhibitory effects of NO on carotid body: Contribution of neural and endothelial nitric oxide synthase isoforms. American Journal of Physiology — Lung Cellular and Molecular Physiology, vol. 284, no. 1, pp. L57–L68. https://www.doi.org/10.1152/ajplung.00494 (In English)
Wang, X., Wang, B.-R., Duan, X.-L. et al. (2002) Strong expression of interleukin-1 receptor type I in the rat carotid body. Journal of Histochemistry and Cytochemistry, vol. 50, no. 12, pp. 1677–1684. https://www.doi.org/10.1177/002215540205001213 (In English)
Wang, X., Zhang, X.-J., Xu, Z. et al. (2006) Morphological evidence for existence of IL-6 receptor alpha in the glomus cells of rat carotid body. Anatomical Record, The Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology, vol. 288A, no. 3, pp. 292–296. https://www.doi.org/10.1002/ar.a.20310 (In English)
Watanabe, T., Tan, N., Saiki, Y. et al. (1996) Possible involvement of glucocorticoids in the modulation of interleukin- 1-induced cardiovascular responses in rats. The Journal of Physiology, vol. 491, no. 1, pp. 231–239. https://www.doi.org/10.1113/jphysiol.1996.sp021211 (In English)
Published
Issue
Section
License
Copyright (c) 2021 Anna A. Klinnikova, Nina P. Aleksandrova
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The work is provided under the terms of the Public Offer and of Creative Commons public license Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). This license allows an unlimited number of persons to reproduce and share the Licensed Material in all media and formats. Any use of the Licensed Material shall contain an identification of its Creator(s) and must be for non-commercial purposes only.
