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NO signaling was assessed by measuring L\u2010NAME induced vasoconstriction of the afferent arteriole using the blood perfused juxtamedullary nephron (JMN) preparation. In this preparation, kidneys were perfused with blood from a donor rat on a matching or different diet to that of the kidney donor. Kidney endothelial cells were isolated with magnetic activated cell sorting and HDAC1 activity was measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found HS\u2010induced impaired NO signaling in the afferent arteriole. This was restored by inhibition of HDAC1 with MS\u2010275. Consistent with these findings, HDAC1 activity was increased in kidney endothelial cells. We further found the loss of NO to be dependent upon the diet of the blood donor rather than the diet of the kidney donor and the plasma from HS\u2010fed rats to be sufficient to induce impaired NO signaling. This indicates the presence of a humoral factor we termed plasma\u2010derived endothelial dysfunction mediator (PDEM). Pretreatment with the antioxidants, PEG\u2010SOD and PEG\u2010catalase, as well as the NOS cofactor, tetrahydrobiopterin, restored NO signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We conclude that HS activates endothelial HDAC1 through PDEM leading to decreased NO signaling. This study provides novel insights into the molecular mechanisms by which a HS decreases renal microvascular endothelial NO signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.14201","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T08:25:52Z","timestamp":1721031952000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endothelial histone deacetylase 1 activity impairs kidney microvascular\n                    <scp>NO<\/scp>\n                    signaling in rats fed a high\u2010salt diet"],"prefix":"10.1111","volume":"240","author":[{"given":"Luke S.","family":"Dunaway","sequence":"first","affiliation":[{"name":"Section of Cardio\u2010Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony K.","family":"Cook","sequence":"additional","affiliation":[{"name":"Section of Cardio\u2010Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailin E.","family":"Kellum","sequence":"additional","affiliation":[{"name":"Section of Cardio\u2010Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Edell","sequence":"additional","affiliation":[{"name":"Section of Cardio\u2010Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3926-0662","authenticated-orcid":false,"given":"Davide","family":"Botta","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Heersink School of Medicine, Immunology Institute The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A.","family":"Molina","sequence":"additional","affiliation":[{"name":"Section of Cardio\u2010Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randee S.","family":"Sedaka","sequence":"additional","affiliation":[{"name":"Section of Cardio\u2010Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, Heersink School of Medicine The University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livius V.","family":"d'Uscio","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvonimir S.","family":"Katusic","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Pollock","sequence":"additional","affiliation":[{"name":"Section of Cardio\u2010Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, 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