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Patients with OSA and IH-treated rodents exhibit heightened sympathetic nerve activity and hypertension. Previous studies reported transcriptional activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) by HIF-1 (hypoxia-inducible factor-1) contribute to autonomic dysfunction in IH-treated rodents. Lysine acetylation, regulated by KATs (lysine acetyltransferases) and KDACs (lysine deacetylases), activates gene transcription and plays an important role in several physiological and pathological processes. This study tested the hypothesis that acetylation of HIF-1\u03b1 by p300\/CBP (CREB-binding protein) (KAT) activates Nox transcription, leading to sympathetic activation and hypertension. Experiments were performed on pheochromocytoma-12\u2009cells and rats treated with IH. IH increased KAT activity, p300\/CBP protein, HIF-1\u03b1 lysine acetylation, HIF-1 transcription, and HIF-1 binding to the Nox4 gene promoter in pheochromocytoma-12\u2009cells, and these responses were blocked by CTK7A, a selective p300\/CBP inhibitor. Plasma norepinephrine (index of sympathetic activation) and blood pressures were elevated in IH-treated rats. These responses were associated with elevated p300\/CBP protein, HIF-1\u03b1 stabilization, transcriptional activation of Nox2 and Nox4 genes, and reactive oxygen species, and all these responses were absent in CTK7A-treated IH rats. These findings suggest lysine acetylation of HIF-1\u03b1 by p300\/CBP is an important contributor to sympathetic excitation and hypertension by IH.<\/jats:p>","DOI":"10.1165\/rcmb.2022-0481oc","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T12:25:04Z","timestamp":1698150304000},"page":"110-118","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":28,"title":["P300\/CBP Regulates HIF-1\u2013Dependent Sympathetic Activation and Hypertension by Intermittent Hypoxia"],"prefix":"10.1093","volume":"70","author":[{"given":"Ning","family":"Wang","sequence":"first","affiliation":[{"name":"Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, The University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Su","sequence":"additional","affiliation":[{"name":"Institute for Integrative Physiology and Center for 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