Obstructive sleep apnoea (OSA) is recognized as an independent risk factor for hypertension. Among disturbances produced by OSA, chronic intermittent hypoxia (CIH) is considered the main factor for hypertension. Although the link between CIH and hypertension is well known, the mechanisms responsible for the hypertension are not entirely known. It has been proposed that CIH produces oxidative stress, inflammation, and sympathetic hyperactivity, which contributes to the hypertension. However, a growing body of evidence show that carotid body (CB) chemoreceptors play a crucial role in the augmented sympathetic drive and the hypertension. We aimed to determine whether peroxynitrite (ONOO-) formation contributes to enhance the CB chemosensory activity and the hypertension during CIH exposure. Accordingly, we study the effects of Ebselen, a specific ONOO- scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir) in the CB and the chemosensory discharges in rats exposed to CIH. In addition, we tested whether chronic treatment with Ebselen may reverse the CIH-induced hypertension. Experimental procedures were approved by the Bio-ethical Committee of the Biological Sciences Faculty, P. Universidad Católica de Chile, and were performed according to the National Institutes of Health Guide, USA. Male Sprague-Dawley rats (200g) were implanted with indwelling catheter for radiotelemetric BP measurements. After one week of recovery, rats were exposed to CIH (5% O2, 12 times/h for 8 h) for 7 days. Then, rats received either Ebselen (10 mg/kg day) or vehicle treatment (DMSO in saline) via subcutaneous implantation of osmotic pumps while the animals continue to be exposed to CIH for 7 days. At the end of the experiments, under sodium pentobalbitone (40 mg/Kg i.p.) anesthesia the CB chemosensory response to hypoxia was recorded, and then rats were perfused with paraformaldehyde 4% for 3-NT-ir assay. Exposure to CIH increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, and produces diurnal hypertension. Ebselen treatment produced a significant reduction in CB 3-NT-ir levels (60.8±14.9 vs. 22.9±4.2 a.u., CIH+veh vs. CIH+Ebs, respectively; p <0.05), reduced the potentiated CB chemosensory response to 5% O2 (266.5±13.4 vs. 168.6±16.8 Hz, CIH+veh vs. CIH+Ebs, respectively; p < 0.05) and reversed the elevated mean BP (116.9±13.2 vs. 82.1±5.1 mmHg, CIH+veh vs. CIH+Ebs, respectively; p< 0.05). Thus, Ebselen prevented the CIH-induced CB chemosensory potentiation and reversed the elevated BP, suggesting that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO- formation.