Alterations in Carotid Body Morphology and Cellular Mechanism Under the Influence of Intermittent Hypoxia

Abstract

Aims: Intermittent hypoxia (IH) training is said to have a preconditioning effect for evoking acclimatization at high altitude (HA). Carotid body (CB) plays a vital role in oxygen sensing and is an important component in HA acclimatization. The present study reports the mechanistic effects of IH that involves episodes of hypoxia of few hours continued for several days, on the CB responses to acute hypobaric hypoxia in terms of morphological changes in CB and its cellular functions. Methodology: 24 Sprague-Dawley (250-300g) rats were divided into 2 major groups: 1) control, 2) experimental group (n=12 each) in which the rats were exposed to IH training for 10 days with a single hypoxic episode of 4h/day at a simulated altitude of 15000ft. 6 rats from each group were further subjected to a simulated hypobaric acute hypoxic (AH) challenge of 1hr at 25000ft to see the effect of IH training (IHT) and were named as 3) Control+ AH challenge and 4) IHT+ AH challenge. Morphological changes in CB in different groups were observed along with expression of hypoxia inducible factor (HIF) 1α, HIF2α, NADPH Oxidase 2 (NOX2) and Superoxide Dismutase 2 (SOD2) using immunohistochemistry for the first time. Results: The results showed that IH training leads to morphological changes in terms of hyperplasia and unaltered HIF1α levels along with a highly significant rise in HIF2α in CB. When the rats are exposed to AH without IH conditioning, there is a significant rise in HIF1α and thus NOX2 levels. However, prior exposure to IH leads to a significant rise in the HIF2α levels and thus SOD2 levels, when subjected to AH challenge. Discussion and Conclusion: These results indicate that IH training affects the cellular response of CB by regulating balanced expression of both HIF1α and HIF2α, thus modulating the cellular redox state by promoting the antioxidant enzyme production and suppressing the pro-oxidant enzyme levels, thereby playing a crucial role in pre-conditioning to acute hypoxia.