Chronic hypoxia upregulates the expression and function of AT(1) 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 AT 1 and AT 2 , in the carotid body. The mRNA expression for subtypes of the AT 1 receptor, AT 1a and AT 1b , was significantly increased in the carotid body with chronic hypoxia. To further investigate the localization of the AT 1 receptor, an immunohistochemical study was performed. The results showed that AT 1 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 AT 1 receptor-mediated excitation of carotid body chemoreceptor activity. These data suggest that chronic hypoxia upregulates the transcriptional and post-transcriptional expression of AT 1 receptors in the rat carotid body. The upregulation of the expression also enhances AT 1 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.

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

“…Accounting that, the simultaneous accumulation of AT 1 mRNA and AT 1 receptors indicates that hypoxia-induced transcriptional mechanisms may activate the AT 1 gene via a hypoxia-response DNA element. This hypothesis is supported by previous reports of an activation of the AT 1 gene in the rat aorta under hypoxic condition (16) and the presence in the AT 1 gene promoter of an AP1 response element (12) that would respond to hypoxia (40). Regarding AT 2 , our finding of ventricular changes during the late stage of hypoxia, but not in the MCTtreated rat, suggests that AT 2 expression regulation might be associated with hypoxia-rather than overload-induced responses.…”

Angiotensin-converting enzyme genotype and the ventilatory responseto exertional hypoxia

“…Within the carotid body itself, responses to hypoxia are mediated by glomus type-I cells [20], which are known to express AT1 receptors [13]. The expression of these receptors is increased as part of the adaptive process to chronic hypoxia [12], consistent with the suggestion that local chemoreceptor RAS may play a role in mediating hypoxic ventilatory responses. However, the role of such glomus AT1 receptors in the transduction of responses to acute hypoxic exercise remain to be elucidated.…”

“…At altitude, diminished alveolar oxygen tensions lead to lower arterial oxygen tensions. However, the fall in oxygen availability with altitude is sensed by carotid bodies that contain hypoxia-sensitive AngII type-1 (AT1) receptors [12,13], driving an increase in minute ventilation (V9E). This compensatory increase in alveolar ventilation (the hypoxic ventilatory response; HVR), helps sustain arterial oxygen saturations (Sa,O 2 ) and tissue oxygen delivery.…”

Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas

“…Hypoxic stress is known to be one such factor which may lead to changes of tissue RAS expression in, for example, the kidney (Neylon et al 1996), the lung (Morrell et al 1995), the carotid body (Leung et al 2000b), the epididymis (Leung et al 2001) and the heart (Morrell et al 1997). These data suggest that tissue RAS is differentially affected by hypoxia and is intimately involved in both the physiology and pathophysiology of the respective tissues.…”