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

THE mammalian carotid body (CB) contains O-2-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% O-2), 2-day exposure to ET-1 (10-1000 nM) caused a dose-dependent increase in BrdU uptake which peaked (similar to 55% of TH+ cells) at around 500 nM ET-1. In chronic hypoxia (5% O-2) alone, BrdU uptake was stimulated (similar to 46% of TH+ cells) relative to normoxia (similar to 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 ETA receptors. (C) 1999 Lippincott Williams & Wilkins.