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Mice lacking functional Npr1 (coding for GC-A\/NPRA) exhibit hypertension and congestive heart failure. However, the underlying mechanisms remain largely less clear. The objective of the present study was to determine the physiological efficacy and impact of all- trans-retinoic acid (ATRA) and sodium butyrate (NaBu) in ameliorating the renal fibrosis, inflammation, and hypertension in Npr1 gene-disrupted haplotype (1-copy; +\/\u2212) mice (50% expression levels of NPRA). Both ATRA and NaBu, either alone or in combination, decreased the elevated levels of renal proinflammatory and profibrotic cytokines and lowered blood pressure in Npr1<jats:sup>+\/\u2212<\/jats:sup>mice compared with untreated controls. The treatment with ATRA-NaBu facilitated the dissociation of histone deacetylase (HDAC) 1 and 2 from signal transducer and activator of transcription 1 (STAT1) and enhanced its acetylation in the kidneys of Npr1<jats:sup>+\/\u2212<\/jats:sup>mice. The acetylated STAT1 formed a complex with nuclear factor-\u03baB (NF-\u03baB) p65, thereby inhibiting its DNA-binding activity and downstream proinflammatory and profibrotic signaling cascades. The present results demonstrate that the treatment of the haplotype Npr1<jats:sup>+\/\u2212<\/jats:sup>mice with ATRA-NaBu significantly lowered blood pressure and reduced the renal inflammation and fibrosis involving the interactive roles of HDAC, NF-\u03baB (p65), and STAT1. The current findings will help in developing the molecular therapeutic targets and new treatment strategies for hypertension and renal dysfunction in humans.<\/jats:p>","DOI":"10.1152\/ajprenal.00166.2017","type":"journal-article","created":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:20:18Z","timestamp":1496276418000},"page":"F781-F795","source":"Crossref","is-referenced-by-count":94,"title":["Inhibition of HDAC enhances STAT acetylation, blocks NF-\u03baB, and suppresses the renal inflammation and fibrosis in<i>Npr1<\/i>haplotype male mice"],"prefix":"10.1152","volume":"313","author":[{"given":"Prerna","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Physiology, Tulane University Health Sciences Center, School of Medicine, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkateswara R.","family":"Gogulamudi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Tulane University Health 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