Erythropoietin potentiates EDHF-mediated dilations in rat middle cerebral arteries

Nadeem Shafi, Jon Andresen, Sean P. Marrelli, Robert M. Bryan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The neuroprotective effects of exogenous erythropoietin (EPO) in animals and humans after brain injury may be afforded, in part, by the influence of EPO on cerebral arteries. We tested (1) if EPO itself is vasoactive and (2) if EPO enhances endothelium-mediated dilations, specifically those mediated by endothelium-derived hyperpolarizing factor (EDHF). Immunoblotting and reverse transcriptasepolymerase chain reaction (RT-PCR) were used to detect EPO receptor. Rat middle cerebral arteries (MCAs) were isolated, pressurized, and perfused in vitro. EPO was directly applied to MCAs to test its vasoactivity. Endothelium-mediated dilations were elicited by UTP, whereas EDHF-mediated dilations were elicited by UTP after inhibition of endothelial nitric oxide synthase and cyclooxygenase. mRNA and protein for EPO receptor was found in rat MCA. Abluminal application of 0.001-10 U/mL EPO, which is selective for vascular smooth muscle, did not alter vessel diameter. In contrast, luminal application of EPO, which is selective for endothelium, resulted in concentration-dependent dilations of up to 39 ± 16% at 10 U/mL (p = 0.0018), though responses were variable. A single dose of EPO (1,000 U/kg) administered to rats 24 h prior to examining vascular function potentiated dilations to UTP 2.6-fold (p < 0.0001). EDHF-mediated dilations were potentiated 2.1-fold following in vivo EPO treatment (p = 0.0034). This study demonstrates that EPO can directly dilate rat MCAs via the endothelium, though not all vessels are responsive. Additionally, pre-treatment with EPO for 24 h in vivo potentiates endothelium-mediated dilations, specifically those mediated by EDHF. Thus, enhanced endothelium-mediated dilations may partially underlie the neuroprotective effects of EPO after brain injury.

Original languageEnglish (US)
Pages (from-to)257-265
Number of pages9
JournalJournal of Neurotrauma
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2008

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Middle Cerebral Artery
Erythropoietin
Endothelium
Dilatation
Uridine Triphosphate
Erythropoietin Receptors
Neuroprotective Agents
Brain Injuries
Cerebral Arteries
Nitric Oxide Synthase Type III
Prostaglandin-Endoperoxide Synthases
Vascular Smooth Muscle
Immunoblotting
Blood Vessels

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Neuroscience(all)

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Erythropoietin potentiates EDHF-mediated dilations in rat middle cerebral arteries. / Shafi, Nadeem; Andresen, Jon; Marrelli, Sean P.; Bryan, Robert M.

In: Journal of Neurotrauma, Vol. 25, No. 3, 01.03.2008, p. 257-265.

Research output: Contribution to journalArticle

Shafi, Nadeem ; Andresen, Jon ; Marrelli, Sean P. ; Bryan, Robert M. / Erythropoietin potentiates EDHF-mediated dilations in rat middle cerebral arteries. In: Journal of Neurotrauma. 2008 ; Vol. 25, No. 3. pp. 257-265.
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