alexa Role of oxidative stress-induced endothelin-converting enzyme activity in the alteration of carotid body function by chronic intermittent hypoxia.


Journal of Pulmonary & Respiratory Medicine

Author(s): Peng YJ, Nanduri J, Raghuraman G, Wang N, Kumar GK,

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Abstract Chronic intermittent hypoxia (CIH) leads to remodelling of the carotid body function, manifested by an augmented sensory response to hypoxia and induction of sensory long-term facilitation (LTF). It was proposed that endothelin-1 (ET-1) contributes to CIH-induced hypoxic hypersensitivity of the carotid body. The objectives of the present study were as follows: (i) to delineate the mechanisms by which CIH upregulates ET-1 expression in the carotid body; and (ii) to assess whether ET-1 also contributes to sensory LTF. Experiments were performed on adult, male rats exposed to alternating cycles of 5\% O2 (15 s) and room air (5 min), nine episodes per hour and 8 h per day for 10 days. Chronic intermittent hypoxia increased ET-1 levels in glomus cells without significantly altering prepro-endothelin-1 mRNA levels. The activity of endothelin-converting enzyme increased with concomitant elevation of ET-1 levels in CIH-exposed carotid bodies, and MnTMPyP, a membrane-permeable antioxidant, prevented these effects. Hypoxia facilitated ET-1 release from CIH-treated carotid bodies, which is a prerequisite for activation of ET receptors; however, hypoxia had no effect on ET-1 release from control carotid bodies. In CIH-exposed carotid bodies, mRNAs encoding ETA receptor were upregulated, and an ETA receptor-specific antagonist abolished CIH-induced hypersensitivity of the hypoxic response, whereas it had no effect on the sensory LTF. These results suggest that ECE-dependent increased production of ET-1 coupled with hypoxia-evoked ET-1 release and the ensuing ETA receptor activation mediate the CIH-induced carotid body hypersensitivity to hypoxia, but the ETA signalling pathway is not associated with sensory LTF elicited by CIH.
This article was published in Exp Physiol and referenced in Journal of Pulmonary & Respiratory Medicine

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