Epoetin beta pegol ameliorates flow-mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats.
Cardiovasc Ther
; 35(2)2017 Apr.
Article
em En
| MEDLINE
| ID: mdl-28054454
ABSTRACT
BACKGROUND/AIMS:
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-mediated dilation (FMD) and the relationship between hematopoiesis and FMD in diabetic nephropathy rats.METHODS:
Male Spontaneously Diabetic Torii rats (SDT, 22 weeks old) were used. C.E.R.A. (0.6, 1.2 µg/kg) was administered subcutaneously once every 2 weeks for 8 weeks. At 1 week after last administration (31 weeks old), we assessed FMD in the femoral arteries of anesthetized rats using a high-resolution ultrasound system. FMD was also measured 1 week after single C.E.R.A. treatment (5.0 µg/kg) to examine the influence of hematopoiesis.RESULTS:
Flow-mediated dilation was significantly decreased in SDT rats before the start of C.E.R.A. treatment (22 weeks old). Repeated administration of C.E.R.A. dose-dependently improved FMD in SDT rats (31 weeks old) without changing blood glucose, nitroglycerin-induced vasodilation, or kidney function. Long-term administration of C.E.R.A. improved the state of endothelial nitric oxide synthase uncoupling in the femoral arteries of SDT rats, which showed a positive correlation with FMD. On the other hand, there was no correlation between FMD and Hb or Hct in SDT rats. Furthermore, at 1 week after single administration of C.E.R.A., FMD was not significantly improved although hemoglobin levels were comparable with levels following long-term C.E.R.A.CONCLUSION:
Long-term treatment with C.E.R.A. improved FMD in SDT rats even after onset of endothelial dysfunction.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Vasodilatação
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Endotélio Vascular
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Eritropoetina
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Diabetes Mellitus
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Óxido Nítrico Sintase Tipo III
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Artéria Femoral
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article