Vascular arginase contributes to arteriolar endothelial dysfunction in a rat model of hemorrhagic shock

Robert A. Johnson, William Durante, Teresa Craig, Kelly J. Peyton, John G. Myers, Ronald M. Stewart, Fruzsina K. Johnson

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background:: Hemorrhagic shock causes hypoperfusion of peripheral tissues and promotes endothelial dysfunction, which may lead to further tissue injury. Trauma increases extrahepatic activity of arginase, an enzyme which competes for l-arginine with nitric oxide synthase, and plays a key role in the development of endothelial dysfunction during aging, hypertension, and diabetes. However, the role of arginase in hemorrhage-induced endothelial dysfunction has not been studied. This study tests the hypothesis that arginase inhibition improves endothelial function after hemorrhage. Methods:: Male Sprague-Dawley rats were implanted with indwelling arterial catheters for blood pressure measurements and blood removal. Awake animals were subjected to a 45% fixed volume controlled hemorrhage and blood pressure was monitored. Unbled rats served as controls. Skeletal muscle arterioles were isolated 24 hours after hemorrhage and cannulated in a pressure myograph system. To study endothelial function, arterioles were exposed to constant midpoint, but altered endpoint pressures, to establish graded levels of luminal flow and internal diameter was measured. Results:: Hemorrhage lowered mean arterial pressure that spontaneously recovered to 78% and 88% of baseline in 2 hours and 20 hours, respectively. Vascular arginase II and blood glucose levels were elevated, whereas hemoglobin and insulin levels were decreased 24 hours after blood loss. In posthemorrhage arterioles, flow-induced dilation was abolished. Acute in vitro treatment with an inhibitor of arginase, Nω-hydroxy-nor-l-arginine, restored flow-induced dilation to unbled control levels. Similarly, the arginase and nitric oxide synthase substrate, l-arginine, but not the inactive isomer, d-arginine, restored flow-induced dilation. Conclusions:: These results indicate that arginase contributes to endothelial dysfunction in resistance vessels after significant hemorrhage.

Original languageEnglish (US)
Pages (from-to)384-391
Number of pages8
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume69
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Arginase
  • Arginine
  • Endothelial dysfunction
  • Hemorrhage
  • Shock
  • Vascular tone

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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