{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:00:52Z","timestamp":1775192452059,"version":"3.50.1"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,3,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Oral NaCl produces a greater natriuresis and diuresis than the intravenous infusion of the same amount of NaCl, indicating the existence of a gastro\u2010renal axis. As one of the major natriuretic hormones secreted by both the intestines and the kidney, we hypothesized that renal uroguanylin interacts with dopamine receptors to increase sodium excretion synergistically, an impaired interaction of which may be involved in the pathogenesis of hypertension.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In Wistar\u2010Kyoto rats, the infusion of uroguanylin or fenoldopam (a D\n              <jats:sub>1<\/jats:sub>\n              \u2010like receptor agonist) induced natriuresis and diuresis. Although subthreshold dosages of uroguanylin or fenoldopam had no effect, the coinfusion of subthreshold dosages of those reagents significantly increased sodium excretion. The coinfusion of an antagonist against D\n              <jats:sub>1<\/jats:sub>\n              \u2010like receptors, SCH23390, or an antagonist against uroguanylin, 2\u2010methylthioadenosine triphosphate, prevented the fenoldopam\u2010 or uroguanylin\u2010mediated natriuresis and diuresis in Wistar\u2010Kyoto rats. However, the natriuretic effects of uroguanylin and fenoldopam were not observed in spontaneously hypertensive rats. The uroguanylin\/D\n              <jats:sub>1<\/jats:sub>\n              \u2010like receptor interaction was also confirmed in renal proximal tubule cells. In renal proximal tubule cells from Wistar\u2010Kyoto rats but not spontaneously hypertensive rats, stimulation of either D\n              <jats:sub>1<\/jats:sub>\n              \u2010like receptors or uroguanylin inhibited Na\n              <jats:sup>+<\/jats:sup>\n              \u2010K\n              <jats:sup>+<\/jats:sup>\n              \u2010ATPase activity, an effect that was blocked in the presence of SCH23390 or 2\u2010methylthioadenosine triphosphate. In renal proximal tubule cells from Wistar\u2010Kyoto rats, guanylyl cyclase C receptor (uroguanylin receptor) and D\n              <jats:sub>1<\/jats:sub>\n              receptor coimmunoprecipitated, which was increased after stimulation by either uroguanylin or fenoldopam; stimulation of one receptor increased renal proximal tubule cell membrane expression of the other.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These data suggest that there is synergism between uroguanylin and D\n              <jats:sub>1<\/jats:sub>\n              \u2010like receptors to increase sodium excretion. An aberrant interaction between the renal uroguanylin and D\n              <jats:sub>1<\/jats:sub>\n              \u2010like receptors may play a role in the pathogenesis of hypertension.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022827","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T10:59:22Z","timestamp":1646132362000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic Effect of Uroguanylin and D\n            <sub>1<\/sub>\n            Dopamine Receptors on Sodium Excretion in Hypertension"],"prefix":"10.1161","volume":"11","author":[{"given":"Cindy","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Cardiology of Chongqing General Hospital Cardiovascular Research Center of Chongqing CollegeUniversity of Chinese Academy of Sciences Chongqing P. R. 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijia","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Cardiology of Chongqing General Hospital Cardiovascular Research Center of Chongqing CollegeUniversity of Chinese Academy of Sciences Chongqing P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-9930","authenticated-orcid":false,"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital The Third Military Medical University Chongqing P. R. China"},{"name":"Chongqing Key Laboratory for Hypertension Research Chongqing Cardiovascular Clinical Research Center Chongqing Institute of Cardiology Chongqing P. R. 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