Expression and Immunolocalization of Endothelin Peptides and Its Receptors, ET_A and ET_B, in the Carotid Body Exposed to Chronic Intermittent Hypoxia

Abstract

Increased levels of endothelin-1 (ET-1) in the carotid body (CB) contribute to the enhancement of chemosensory responses to acute hypoxia in cats exposed to chronic intermittent hypoxia (CIH). However, it is not known if the ET receptor types A (ETA-R) and B (ETB-R) are upregulated. Thus, we studied the expression and localization of ETA-R and ETB-R using Western blot and immunohistochemistry (IHC) in CBs from cats exposed to cyclic hypoxic episodes, repeated during 8 hr for 4 days. In addition, we determined if ET-1 is expressed in the chemoreceptor cells using double immunofluorescence for ET-1 and tyrosine hydroxylase (TH). We found that ET-1 expression was ubiquitous in the blood vessels and CB parenchyma, although double ET-1 and TH-positive chemoreceptor cells were mostly found in the parenchyma. ETAR was expressed in most chemoreceptor cells and blood vessels of the CB vascular pole. ETB-R was expressed in chemoreceptor cells, parenchymal capillaries, and blood vessels of the vascular pole. CIH upregulated ETB-R expression by approximately 2.1 (Western blot) and 1.6-fold (IHC) but did not change ETA-R expression. Present results suggest that ET-1,ETA-R, and ETB-R are involved in the enhanced CB chemosensory responses to acute hypoxia induced by CIH.

Oxidative Stress in the Carotid Body: Implications for the Cardioventilatory Alterations Induced by Obstructive Sleep Apnea

“…It is known that the plasmatic ET-1 level increases in rats exposed to intermittent hypoxia (Kanagy et al, 2001) and OSA patients (Phillips et al, 1999). This potent vasoconstrictor peptide is expressed in the endothelium, blood vessels and glomus cells of the carotid body (Rey et al, 2007). The application of ET-1 produces chemosensory excitation in both in situ and in vitro carotid body perfused preparations, but not in the superfused preparation devoid of vascular effects .…”

Arterial Chemoreceptors and Sympathetic Nerve Activity

“…67 ET-1 immunostaining in the CB vasculature and glomus cells is increased in cats exposed to CIH, whereas ET-1 plasma levels are unchanged. 68 A nonselective ET receptor antagonist, bosentan, reduces the elevated normoxic and hypoxic CB discharge induced by CIH. 67 Upregulation of both ET-1 expression and enhanced superoxide anion signaling in the CB in response to CIH appears to be related to activation of hypoxia-inducible factor-1 63,69 and/or activator protein-1.…”

Cardiovascular risk factors regulate the expression of vascular endothelin receptors

“…These data suggest that vascular hypoxia due to reduced blood flow by vascular spasm and/or obstruction in ischemic CVD may contribute to an alteration of endothelin receptors. Chronic intermittent hypoxia increased the expression of ET B receptors in the carotid body (Rey et al, 2007). Increased ET B receptor expression has also been seen in blood vessels of patients with ischemic heart disease (Wackenfors et al, 2004) and after experimental ischemic stroke in rats (Stenman et al, 2002).…”