Abstract
The carotid body (CB) plays important roles in cardiorespiratory changes in intermittent hypoxia (IH). Erythropoietin (EPO), a hypoxia-inducible factor (HIF)-1 target gene, is present in the chemoreceptive type-I cells in the CB but its expression and role in IH resembling sleep apnoeic conditions are not known. We hypothesized that IH upregulates the expression of EPO and its receptor (EPOr) in the rat CB. The CB expressions of EPO and EPOr were examined in rats breathing 10% O2 (in isobaric chamber for CH, 24 hour/day) or in IH (cyclic between air and 5% O2 per minute, 8 hour/day) for 3–28 days. Immunohistochemical studies revealed that the EPO and EPOr proteins were localized in CB glomic clusters. The proportional amount of cells with positive staining of EPO immunoreactivities was significantly increased in both IH and CH groups when compared with the normoxic control. The EPO expression was more markedly increased in the CH than that of the IH groups throughout the time course, reaching a peak level at day 14. The positive EPOr immunostaining was increased significantly in the 3-day CH group. By day 14, the EPOr expression elevated considerably at peak levels in both IH and CH rats, whereas the elevation was greater in the CH rats. These results suggest an upregulation of EPO and its receptor expression in the rat CB under IH and CH conditions, presumably mediated by the activation of HIF-1 pathway. The increased EPO binding to its receptor might play a role in the enhancement of CB excitability during the early pathogenesis in patients with sleep-disordered breathing.
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References
Bee, D., and Howard, P., 1993, The carotid body: a review of its anatomy, physiology and clinical importance, Monaldi Arch Chest Dis 48(1):48–53.
Chen, Y., Tipoe, G. L., Liong, E., Leung, S., Lam, S. Y., Iwase, R., Tjong, Y. W., and Fung, M. L., 2002, Chronic hypoxia enhances endothelin-1-induced intracellular calcium elevation in rat carotid body chemoreceptors and up-regulates ETA receptor expression, Pflugers Arch 443(4):565–573.
Fletcher, E. C., 2001, Invited review: Physiological consequences of intermittent hypoxia: systemic blood pressure, J Appl Physiol 90(4):1600–1605.
Fung, M. L., 2003, Hypoxia-inducible factor-1: a molecular hint of physiological changes in the carotid body during long-term hypoxemia? Curr Drug Targets Cardiovasc Haematol Disord 3(3):254–259.
Gonzalez, C., Almaraz, L., Obeso, A., and Rigual, R., 1994, Carotid body chemoreceptors: from natural stimuli to sensory discharges, Physiol Rev 74(4):829–98.
Heath, D., Edwards, C., and Harris, P., 1970, Post-mortem size and structure of the human carotid body, Thorax 25(2):129–140.
Jelkmann, W., 1992, Erythropoietin: structure, control of production, and function, Physiol Rev 72(2):449–489.
Kim, D. K., Natarajan, N., Prabhakar, N. R., and Kumar, G. K., 2004, Facilitation of dopamine and acetylcholine release by intermittent hypoxia in PC12 cells: involvement of calcium and reactive oxygen species, J Appl Physiol 96(3):1206–1215; discussion 1196.
Lam, S. Y., Tipoe, G. L., Liong, E. C., and Fung, M. L., 2008, Differential expressions and roles of hypoxia-inducible factor-1alpha, -2alpha and -3alpha in the rat carotid body during chronic and intermittent hypoxia, Histol Histopathol 23(3):271–280.
Pagel, H., Engel, A., and Jelkmann, W., 1992, Erythropoietin induction by hypoxia. A comparison of in vitro and in vivo experiments, Adv Exp Med Biol 317:515–519.
Peng, Y. J., Rennison, J., and Prabhakar, N. R., 2004, Intermittent hypoxia augments carotid body and ventilatory response to hypoxia in neonatal rat pups, J Appl Physiol 97(5):2020–2025.
Prabhakar, N. R., 2001, Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms, J Appl Physiol 90(5):1986–1994.
Soliz, J., Joseph, V., Soulage, C., Becskei, C., Vogel, J., Pequignot, J. M., Ogunshola, O., and Gassmann, M., 2005, Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies, J Physiol 568(Pt 2):559–571.
Soliz, J., Soulage, C., Hermann, D. M., and Gassmann, M., 2007, Acute and chronic exposure to hypoxia alters ventilatory pattern but not minute ventilation of mice overexpressing erythropoietin, Am J Physiol Regul Integr Comp Physiol 293(4):R1702–R1710.
Tipoe, G. L., and Fung, M. L., 2003, Expression of HIF-1alpha, VEGF and VEGF receptors in the carotid body of chronically hypoxic rat, Respir Physiol Neurobiol 138(2–3):143–154.
Tramezzani, J. H., Morita, E., and Chiocchio, S. R., 1971, The carotid body as a neuroendocrine organ involved in control of erythropoiesis, Proc Natl Acad Sci USA 68(1):52–55.
Wang, G. L., Jiang, B. H., Rue, E. A., and Semenza, G. L., 1995, Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension, Proc Natl Acad Sci USA 92(12):5510–5514.
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Lam, S., Tipoe, G., Fung, M. (2009). Upregulation of Erythropoietin and its Receptor Expression in the Rat Carotid Body During Chronic and Intermittent Hypoxia. In: Gonzalez, C., Nurse, C.A., Peers, C. (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 648. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2259-2_24
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DOI: https://doi.org/10.1007/978-90-481-2259-2_24
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