{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T17:03:25Z","timestamp":1769015005407,"version":"3.49.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T00:00:00Z","timestamp":1581984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"PDBCEx COLDOC 679"},{"DOI":"10.13039\/100007637","name":"COLCIENCIAS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p\/>\n               <jats:sec>\n                  <jats:title>OBJECTIVES<\/jats:title>\n                  <jats:p>Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration\u2013response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency\u2013response and concentration\u2013response curves to phenylephrine were performed in the absence and presence of endothelial factors inhibitors and K+ channel blockers. Endothelial nitric oxide synthase, \u03b11 adrenergic receptor and large conductance Ca2+-activated K+ channel protein expressions were measured by Western blotting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Ranolazine (10\u22129\u201310\u22124 M) produced a concentration-dependent relaxation only in rings precontracted with phenylephrine that was reduced by endothelial denudation, NG-nitro-l-arginine methyl ester (10\u22124 M), charybdotoxin (10\u22127 M) and verapamil (10\u22126 M). Ranolazine diminished adrenergic contractions induced by electrical field stimulation (2\u20134\u2009Hz) and phenylephrine (10\u22129\u201310\u22125 M) that were prevented by tetraethylammonium (10\u22123 M) and charybdotoxin (10\u22127 M). Ranolazine significantly decreased \u03b11 adrenergic receptor and increased large conductance Ca2+-activated K+ channel protein expression in the saphenous vein.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Ranolazine diminishes the adrenergic vasoconstriction, acting as \u03b11 antagonist, and by increasing large conductance Ca2+-activated K+ channel involvement. The relaxant effects of ranolazine are partially mediated by endothelial nitric oxide, large conductance Ca2+-activated K+ channels and the blockade of voltage-dependent Ca2+ channels.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejcts\/ezaa034","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T20:09:02Z","timestamp":1579291742000},"page":"277-285","source":"Crossref","is-referenced-by-count":7,"title":["Relaxant and antiadrenergic effects of ranolazine in human saphenous vein"],"prefix":"10.1093","volume":"58","author":[{"given":"Patricia","family":"Marchio","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Valencia and Institute of Health Research INCLIVA, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sol","family":"Guerra-Ojeda","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Valencia and Institute of Health Research INCLIVA, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mart\u00edn","family":"Aldasoro","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Valencia and Institute of Health Research INCLIVA, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soraya Lilian","family":"Valles","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Valencia and Institute of Health Research INCLIVA, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iv\u00e1n","family":"Mart\u00edn-Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Hospital of Vinalopo, Elche, Spain"},{"name":"Department of Surgery, School of Medicine, University of Valencia, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Bautista","family":"Mart\u00ednez-Le\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, University of Valencia, Valencia, Spain"},{"name":"Department of Cardiac Surgery, University General Hospital of Valencia, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Dolores","family":"Mauricio","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Valencia and Institute of Health Research INCLIVA, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Maria","family":"Vila","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, University of Valencia and Institute of Health Research INCLIVA, Valencia, 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