Role of ET-1 in hypoxia-induced mitosis of cultured rat carotid body chemoreceptors

• Published in: Neuroreport Vol. 10; no. 18; p. 3739
• Main Authors: Paciga, M, Vollmer, C, Nurse, C
• Format: Journal Article
• Language: English
• Published: England 16.12.1999
• Subjects: Animals; Bromodeoxyuridine - metabolism; Carotid Body - drug effects; Carotid Body - pathology; Cell Survival - drug effects; Cells, Cultured; Chemoreceptor Cells - drug effects; Chemoreceptor Cells - pathology; Chronic Disease; Endothelin-1 - pharmacology; Endothelin-1 - physiology; Hypoxia - metabolism; Hypoxia - physiopathology; Mitosis; Rats; Receptor, Endothelin A; Receptors, Endothelin - physiology; Reference Values
• ISSN: 0959-4965; 1473-558X
• DOI: 10.1097/00001756-199912160-00003

The mammalian carotid body (CB) contains O2-chemoreceptors, i.e. glomus cells, which display increased mitoses and endothelin-1 (ET-1) expression during chronic hypoxia. To investigate whether endogenous ET-1 might mediate these mitogenic effects, we quantified bromodeoxyuridine (BrdU) uptake by tyrosine hydroxylase (TH)-positive glomus cells in rat CB cultures using double-label immunofluorescence. In normoxia (20% O2), 2-day exposure to ET-1 (10-1000 nM) caused a dose-dependent increase in BrdU uptake which peaked (approximately 55% of TH+ cells) at around 500 nM ET-1. In chronic hypoxia (5% O2) alone, BrdU uptake was stimulated (approximately 46% of TH+ cells) relative to normoxia (approximately 30%), but the effect was abolished in the presence of specific (BQ 123) or non-specific (PD 142893) ETA receptor antagonists (10(-5) M). Thus paracrine/autocrine release of ET-1 in the hypoxic carotid body may promote glomus cell mitosis via ET(A) receptors.