Contribution of endothelin-1 to the enhanced carotid body chemosensory responses induced by chronic intermittent hypoxia.
Chronic intermittent hypoxia (CIH) enhances carotid body (CB) chemosensory responses to acute hypoxia. We tested the hypothesis that endothelin-1 (ET-1), an excitatory modulator of CB chemoreception may contribute to the enhanced CB chemosensory responses in cats exposed to cyclic hypoxic episodes repeated during 8 h for 4 days. Accordingly, we measured the ET-1 immunoreactivity (ET-ir) in the CB and plasma. Using a perfused CB preparation, we studied the effects of exogenous ET-1 and bosentan, a non-selective endothelin receptor type A and B antagonist, on the frequency of chemosensory discharges (f(x)) during normoxia, mild and severe hypoxia. We found that CIH increased ET-ir in the CB by approximately 10-fold leaving ET-1 plasma levels unchanged. Application of ET-1 to control and CIH-treated CBs produced long-lasting dose-dependent increases in f(x), although the dose-response curve showed a rightward-shift in the CIH-treated CBs. CIH increased baseline f(x) and hypoxic chemosensory responses, which were reduced by 50 microM bosentan in CBs from CIH-treated cats. Present results suggest that a local increase of ET-1 in the CB may contribute to the enhanced chemosensory responses induced by CIH predominantly through a vasomotor mechanism.
Rey
Sergio
S
Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago Casilla 114-D, Chile.
Del Rio
Rodrigo
R
Iturriaga
Rodrigo
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000077300:Bosentan; D002344:Carotid Body / Q000187:drug effects* / Q000503:physiopathology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D010100:Oxygen / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000959:Antihypertensive Agents; D019332:Endothelin-1; D013449:Sulfonamides; D000077300:Bosentan; D010100:Oxygen