{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T04:58:01Z","timestamp":1775624281402,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007405","name":"Hjerteforeningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007405","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The epithelial sodium channel (ENaC) is expressed in cultured endothelial cells and inhibitory coupling to eNOS activity has been proposed. The present study tested the hypothesis that ENaC blockers increase systemic NO\u2010products and lower blood pressure in patients and mice, depending on eNOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NO\u2010products and cGMP were measured in diabetes patient urine and plasma samples before and after amiloride treatment (20\u201040\u00a0mg for two days, plasma n\u00a0=\u00a022, urine n\u00a0=\u00a012 and 5\u201010\u00a0mg for eight weeks, plasma n\u00a0=\u00a052, urine n\u00a0=\u00a055). Indwelling catheters were implanted in the femoral artery and vein in mice for continuous arterial blood pressure and heart rate recordings and infusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with amiloride for two days increased plasma and urine NO\u2010products, while plasma cGMP decreased and urinary cGMP was unchanged in patient samples. Eight weeks of treatment with amiloride did not alter NO\u2010products and cGMP. In mice, amiloride boli of 5, 50, and 500\u00a0\u00b5g\/kg lowered heart rate and arterial blood pressure significantly and acutely. Benzamil had no effect on pressure and raised heart rate. In hypertensive eNOS<jats:sup>\u2212\/\u2212<\/jats:sup> and L\u2010NAME\u2010treated mice, amiloride lowered blood pressure significantly. L\u2010NAME infusion significantly decreased NO\u2010products in plasma; amiloride and eNOS\u2010deletion had no effect. An acetylcholine bolus resulted in acute blood pressure drop that was attenuated in eNOS<jats:sup>\u2212\/\u2212<\/jats:sup> and L\u2010NAME mice. ENaC subunit expressions were not detected consistently in human and mouse arteries and endothelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Amiloride has an acute hypotensive action not dependent on ENaC and eNOS and likely related to the heart.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13189","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T02:45:15Z","timestamp":1537584315000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The acute blood pressure\u2010lowering effect of amiloride is independent of endothelial ENaC and eNOS in humans and mice"],"prefix":"10.1111","volume":"225","author":[{"given":"Rikke","family":"Ydegaard","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Renal Research, Institute for Molecular Medicine University of Southern Denmark Odense C Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Renal Research, Institute for Molecular Medicine University of Southern Denmark Odense C Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina S.","family":"Oxlund","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ib A.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille B. 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