{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:00:56Z","timestamp":1775192456003,"version":"3.50.1"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,4,16]]},"abstract":"\n Background<\/jats:title>\n \n Dopamine D\n 5<\/jats:sub>\n receptor (D\n 5<\/jats:sub>\n R) plays an important role in the maintenance of blood pressure by regulating renal sodium transport. Our previous study found that human D\n 5<\/jats:sub>\n R mutant F173L transgenic (\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n \u2010TG) mice are hypertensive. In the present study, we aimed to investigate the mechanisms causing this renal D\n 5<\/jats:sub>\n R dysfunction in\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n \u2010TG mice.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Compared with wild\u2010type D\n 5<\/jats:sub>\n R\u2010TG (\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n WT<\/jats:italic>\n <\/jats:sup>\n \u2010TG) mice,\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n \u2010TG mice have higher blood pressure, lower basal urine flow and sodium excretion, and impaired agonist\u2010mediated natriuresis and diuresis. Enhanced reactive oxygen species production in\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n \u2010TG mice is caused, in part, by decreased expression of antioxidant enzymes, including thioredoxin 1 (Trx1). Na\n +<\/jats:sup>\n \u2010K\n +<\/jats:sup>\n \u2010ATPase activity is increased in mouse renal proximal tubule cells transfected with\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n , but is normalized by treatment with exogenous recombinant human Trx1 protein. Regulation of Trx1 by D\n 5<\/jats:sub>\n R occurs by the phospholipase C\/ protein kinase C (PKC) pathway because upregulation of Trx1 expression by D\n 5<\/jats:sub>\n R does not occur in renal proximal tubule cells from D\n 1<\/jats:sub>\n R knockout mice in the presence of a phospholipase C or PKC inhibitor. Fenoldopam, a D\n 1<\/jats:sub>\n R and D\n 5<\/jats:sub>\n R agonist, stimulates PKC activity in primary renal proximal tubule cells of\n hD5R<\/jats:italic>\n \n WT<\/jats:italic>\n <\/jats:sup>\n \u2010<\/jats:italic>\n TG mice, but not in those of\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n \u2010TG mice. Hyperphosphorylation of hD\n 5<\/jats:sub>\n R\n F173L<\/jats:sup>\n and its dissociation from G\u03b1s and G\u03b1q are associated with impairment of D\n 5<\/jats:sub>\n R\u2010mediated inhibition of Na\n +<\/jats:sup>\n \u2010K\n +<\/jats:sup>\n \u2010ATPase activity in\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n \u2010TG mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These suggest that\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n increases blood pressure, in part, by decreasing renal Trx1 expression and increasing reactive oxygen species production. Hyperphosphorylation of hD\n 5<\/jats:sub>\n R\n F173L<\/jats:sup>\n , with its dissociation from G\u03b1s and G\u03b1q, is the key factor in impaired D\n 5<\/jats:sub>\n R function of\n hD<\/jats:italic>\n \n 5<\/jats:italic>\n <\/jats:sub>\n R<\/jats:italic>\n \n F173L<\/jats:italic>\n <\/jats:sup>\n \u2010TG mice.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.012192","type":"journal-article","created":{"date-parts":[[2019,4,6]],"date-time":"2019-04-06T09:10:07Z","timestamp":1554541807000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Role of Thioredoxin 1 in Impaired Renal Sodium Excretion of\n hD<\/i>\n \n 5<\/i>\n <\/sub>\n R<\/i>\n \n F173L<\/i>\n <\/sup>\n Transgenic Mice"],"prefix":"10.1161","volume":"8","author":[{"given":"Shaoxiong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaorong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro A.","family":"Jose","sequence":"additional","affiliation":[{"name":"Division of Renal Disease & Hypertension Departments of Medicine and Pharmacology\/Physiology The George Washington University School of Medicine and Health Sciences Washington DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition The Third Affiliated Hospital of Chongqing Medical University Chongqing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology Daping Hospital Army Medical University of PLA Chongqing P.R. 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