Chronic hypoxia upregulates the expression and function of AT1 receptor in rat carotid body

Abstract

In the present study, the effects of chronic hypoxia on the expression and localization of angiotensin II (Ang II) receptors are investigated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by immunohistochemistry. The effect of chronic hypoxia on the carotid body chemoreceptor activity was also examined by in vitro electrophysiology. Results from RT-PCR revealed that chronic hypoxia exhibited differential effects on the gene expression of Ang II receptors, namely AT1 and AT2, in the carotid body. The mRNA expression for subtypes of the AT1 receptor, AT1a and AT1b, was significantly increased in the carotid body with chronic hypoxia. To further investigate the localization of the AT1 receptor, an immunohistochemical study was performed. The results showed that AT1 receptor immunoreactivity was found in lobules of glomus cells in the carotid body and the immunoreactivity was more intense in chronic hypoxia than in normoxic controls. In vitro electrophysiological studies consistently demonstrated that chronic hypoxia enhanced the AT1 receptor-mediated excitation of carotid body chemoreceptor activity. These data suggest that chronic hypoxia upregulates the transcriptional and post-transcriptional expression of AT1 receptors in the rat carotid body. The upregulation of the expression also enhances AT1 receptor-mediated excitation of the carotid body afferent activity. This might be important in the modulation of cardiorespiratory functions as well as fluid and electrolyte homeostasis during chronic hypoxia.