{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:24:57Z","timestamp":1753878297621,"version":"3.41.2"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T00:00:00Z","timestamp":1489363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background\/Aims<\/jats:title><jats:p>Patients with diabetic nephropathy have a high cardiovascular mortality. Epoetin beta pegol (continuous erythropoietin receptor activator, C.E.R.A.) is a drug for the treatment of renal anemia. In this study, we investigated the effect of C.E.R.A. on vascular endothelial function as evaluated by flow\u2010mediated dilation (<jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content>) and the relationship between hematopoiesis and <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content> in diabetic nephropathy rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Spontaneously Diabetic Torii rats (<jats:styled-content style=\"fixed-case\">SDT<\/jats:styled-content>, 22\u00a0weeks old) were used. C.E.R.A. (0.6, 1.2\u00a0\u03bcg\/kg) was administered subcutaneously once every 2\u00a0weeks for 8\u00a0weeks. At 1\u00a0week after last administration (31\u00a0weeks old), we assessed <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content> in the femoral arteries of anesthetized rats using a high\u2010resolution ultrasound system. <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content> was also measured 1\u00a0week after single C.E.R.A. treatment (5.0\u00a0\u03bcg\/kg) to examine the influence of hematopoiesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Flow\u2010mediated dilation was significantly decreased in <jats:styled-content style=\"fixed-case\">SDT<\/jats:styled-content> rats before the start of C.E.R.A. treatment (22\u00a0weeks old). Repeated administration of C.E.R.A. dose\u2010dependently improved <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">SDT<\/jats:styled-content> rats (31\u00a0weeks old) without changing blood glucose, nitroglycerin\u2010induced vasodilation, or kidney function. Long\u2010term administration of C.E.R.A. improved the state of endothelial nitric oxide synthase uncoupling in the femoral arteries of <jats:styled-content style=\"fixed-case\">SDT<\/jats:styled-content> rats, which showed a positive correlation with <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content>. On the other hand, there was no correlation between <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content> and Hb or Hct in <jats:styled-content style=\"fixed-case\">SDT<\/jats:styled-content> rats. Furthermore, at 1\u00a0week after single administration of C.E.R.A., <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content> was not significantly improved although hemoglobin levels were comparable with levels following long\u2010term C.E.R.A. treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Long\u2010term treatment with C.E.R.A. improved <jats:styled-content style=\"fixed-case\">FMD<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">SDT<\/jats:styled-content> rats even after onset of endothelial dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12250","type":"journal-article","created":{"date-parts":[[2017,1,5]],"date-time":"2017-01-05T06:56:40Z","timestamp":1483599400000},"source":"Crossref","is-referenced-by-count":2,"title":["Epoetin beta pegol ameliorates flow\u2010mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic 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