Intermittent hypoxia increases AT1 receptor and oxidative stress in the rat carotid body

Abstract

The carotid body (CB) plays an important role in cardiorespiratory changes in intermittent hypoxia. Recent data suggest an involvement of angiotensin II (AT) and reactive oxygen species in the pathophysiological development. The aim of this study was to examine the expression of AT1 receptor and the by-products of oxidative stress in the CB of rats exposed to intermittent hypoxia (IH, cyclic between air and 5% O2 per minute, 8 hour/day) or in isobaric chamber breathing 10% O2 for chronic hypoxia (CH, 24 hour/day) for up to 4 weeks. Immunohistochemical (IHC) studies revealed that, in the IH and CH groups, the immunoreactivity (IR) of AT1 receptor was mainly observed in glomic clusters of the CB. The AT1 receptor expression was markedly elevated in the 3- day IH group but not in the CH, and it reached a plateau at day 7. Also, intracellular calcium response to AT was enhanced in the fura-2 loaded dissociated glomus cells from 3-day IH rats when compared with the normoxic controls. Levels of oxidative stress in the CB were assessed by IHC method using specific antibody against nitrotyrosine (NTR) and ELISA for the detection of total 8-isoprostane (IPT) in the serum. NTR-IR and IPT levels were significantly elevated in 7-day IH group and returned to normoxic levels by day 14, whereas mild expression of NTR and IPT were observed in the CH and normoxic controls throughout the time course. These data suggest that oxidative stress occurred within the first week in the IH but not with the CH group. In conclusion, the upregulation of the AT1 receptor expression may play a role in the enhancement of CB excitability during IH and this is associated with oxidative stress during an early time course. (Supported by research grants from Research Grants Council, HKSAR and the University of Hong Kong)