Abstract
Chelation of iron in in vitro carotid body emulates the effects of hypoxia. The role iron plays in in vivo ventilatory responses is unclear. In the current study we addressed this issue by examining the effects of chronic iron chelation on the hypoxic ventilatory response in 9 conscious Wistar rats. Acute responses to 14 and 9% O2in N2 were recorded in the same rat before and then after 7 and 14 days of continuous iron chelation. Iron chelation was carried out with ciclopirox olamine (CPX) in a dose of 20 mg/kg daily, i.p. Ventilation was recorded with whole body plethysmography. We found that the peak hypoxic ventilation (VE achieved during 14 and 9% hypoxia was lower by 239.6±55.4(SE) and 269.6.2±69.2 ml min-1kg-1, respectively, in the rats treated with CPX for 7 days. The decreases were not intensified by a longer duration of iron chelation. CPX failed to alter hypoxic sensitivity, assessed from the gain of peak VE with increasing strength of the hypoxic stimulus. In conclusion, we believe we have shown that iron is operational in shaping the hypoxic ventilatory response, but is not liable to be the underlying determinant of the hypoxic chemoreflex.
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Baby, S.M., Roy, A., Mokashi, A.M., & Lahiri, S. 2003, Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1α and -1β in the rat carotid body and glomus cells. Histochem Cell Biol, 120: 343–352.
Bel Aiba, R.S. & Görlach, A. 2003, Regulation of the hypoxia-inducible transcription factor HIF-1 by reactive oxygen species in smooth muscle cells. Adv Exp Med Biol, 536: 171–178.
Daudu, P.A., Roy, A., Rozanov, C., Mokashi, A., & Lahiri S. 2002, Extra- and intracellular free iron and the carotid body responses. Respir Physiol Neurobiol, 130: 21–31.
Di Giulio, C., Bianchi, G., Cacchio, M., Artese, L., Rapino, C., Macri, M.A., & Di Ilio, C. 2005, Oxygen and life span: chronic hypoxia as to model for studying HIF-1alpha, VEGF and NOS during aging. Respir Physiol Neurobiol, 147: 31–38.
Hofer, T., Desbaillets, I., Höpfl, G., Gassmann, M., & Wenger, R.H. 2001, Dissecting hypoxia-dependent and hypoxia-independent steps in the HIF-1α activation cascade: implications for HIF-1α gene therapy. FASEB J, 15: 2715–2717.
Jewell. U.R., Kvietikova, I., Scheid, A., Bauer, C., Wenger, R.H. & Gassmann, M. 2001, Induction of HIF-1α in response to hypoxia is instantaneous. FASEB J, 15: 1312–1314.
Lahiri, S., Rozanov, C., Roy, A., Storey, B., & Buerk, D.G. 2001, Regulation of oxygen sensing in peripheral arterial chemoreceptors. Int J Biochem Cell Biol, 33: 755–774.
Linden, T., Katschinski, D.M., Eckhardt, K., Scheid, A., Pagel, H., & Wenger, R.H. 2003, The antimycotic ciclopirox olamine induces HIF-1α stability, VEGF expression, and angiogenesis. FASEB J, 17: 761–763.
Martin-Body, R.L., Robson, G.J., & Sinclair J.D. 1985, Respiratory effects of sectioning the carotid sinus glossopharyngeal and abdominal vagal nerves in the awake rat. J Physiol, 361: 35–45.
Olson, E.B. Jr., Vidruk, E.H., & Dempsey, J.A. 1988, Carotid body excision significantly changes ventilatory control in awake rats. J Appl Physiol, 64: 666–671.
Paddenberg, R., Goldenberg, A., Faulhammer, P., Braun-Dullaeus, R.C., & Kummer, W. 2003, Mitochondrial complex II is essential for hypoxia-induced ROS generation and vasoconstriction in the pulmonary vasculature. Adv Exp Med Biol, 536: 163–169.
Pokorski, M. & Lahiri, S. 1991, Endogenous opiates and ventilatory acclimatization to chronic hypoxia in the cat. Respir Physiol, 83: 211–222.
Roy, A., Li, J., Baby, S.M., Mokashi, A., Burek, D.G., & Lahiri, S. 2004a, Effects of iron-chelators on ion-channels and HIF-1α in the carotid body. Respir Physiol Neurobiol, 141: 115–123.
Roy, A., Volgin, D.V., Baby, S.M., Mokashi, A., Kubin, L. & Lahiri, S. 2004b, Activation of HIF-1α by hypoxia and iron chelation in isolated rat carotid body. Neurosci Lett, 363: 229–232.
Semenza, G.L. 1999, Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Ann Rev Cell Dev Biol, 15: 551–578.
Tipoe, G.L. & Fung, M.L. 2003, Expression of HIF-1α VEGF and VEGF receptors in the carotid body of chronically hypoxic rat. Respir Physiol Neurobiol, 138: 143–154.
Wang, G.L. & Semenza, G.L. 1993, Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: Implications for models of hypoxia signal transduction. Blood, 82: 3610–3615.
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Pokorski, M., Antosiewicz, J., Giulio, C., Lahiri, S. (2009). Iron Chelation and the Ventilatory Response to 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_25
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DOI: https://doi.org/10.1007/978-90-481-2259-2_25
Publisher Name: Springer, Dordrecht
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