Essential role of endothelial nitric oxide synthase in vascular effects of erythropoietin

Livius V. D'Uscio, Leslie A. Smith, Anantha V. Santhanam, Darcy Richardson, Karl A. Nath, Zvonimir S. Katusic

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Erythropoietin (EPO) fosters tissue oxygenation by stimulating erythropoiesis. More recently, EPO has been recognized as a tissue-protective cytokine. In this study, we tested the hypothesis that endothelial NO synthase (eNOS) plays a key role in the vascular protective effect of EPO. A murine model of wire-induced injury of carotid artery was used to examine the effect of EPO on endothelial repair and arterial wall architecture. Recombinant human EPO (1000 U/kg, SC, biweekly) was administered for 2 weeks in wild-type and eNOS-deficient mice after which reactivity of isolated carotid arteries was studied in vitro, and the vasculature was histologically assessed. Injured arteries exhibited impairment of endothelium-dependent relaxations to acetylcholine (P<0.05). This was associated with increased medial cross-sectional area (P<0.05). EPO upregulated expression of phosphorylated Ser1177-eNOS and normalized the vasodilator response to acetylcholine (P<0.05). Furthermore, EPO prevented the injury-induced increase in medial cross-sectional area (P<0.05). The vascular protective effects of EPO were abolished in eNOS-deficient mice. Most notably, EPO significantly increased systolic blood pressure and enhanced medial thickening of injured carotid arteries in eNOS-deficient mice (P<0.05). Our results demonstrate that EPO prevents aberrant remodeling of the injured carotid artery. The protective effects of EPO are critically dependent on activation of eNOS.

Original languageEnglish (US)
Pages (from-to)1142-1148
Number of pages7
JournalHypertension
Volume49
Issue number5
DOIs
StatePublished - May 1 2007

Keywords

  • Endothelium
  • Erythropoietin
  • Mice
  • Nitric oxide synthase
  • Vasculature

ASJC Scopus subject areas

  • Internal Medicine

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