Endothelin-1-Mediated Mechanisms in the Carotid Body Modulates Cardiovascular Responses in Rats Exposed to Chronic Intermittent Hypoxia

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea (OSA), is associated with hypertension. The increased of carotid body (CB) sensitivity due to enhanced sympathetic efferent may be mainly responsible for the elevation of blood pressure. Accordingly, we studied this effect of Endothelin-1 (ET-1)-induced CB chemosensory response to CIH, as a vasoactive peptide expressed in CB. The purpose of this study was to investigate the mean arterial blood pressure (MAP) and renal sympathetic nerve activity (RSNA) responses in CIH group by injecting ET-1 to directly stimulate CB chemoreceptor. Furthermore, whether ET receptor-mediated PKC and p³⁸MAPK signaling pathway was involved in CIH-induced CB activation was also studied. Male Sprague–Dawley rats were exposed to CIH (8 h/day for 3 weeks) and the MAP and RSNA were recorded in CIH rats and Sham rats. Our results demonstrated that ET-1-induced MAP and RSNA increase were mainly mediated by ET_A receptor activation in CB chemosensory after CIH exposure. Moreover, P³⁸MAPK and PKC signaling pathway might be involved in ET-1-induced increase of MAP and RSNA in CIH group, which provided a potential therapeutic target of OSA.