Arginase depletes plasma l-arginine and decreases pulmonary vascular reserve during experimental pulmonary embolism

John A. Watts, Michael A. Gellar, Mary Beth K. Fulkerson, Sudeep K. Das, Jeffrey A. Kline

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The experiments test if experimental PE causes red blood cell hemolysis, arginase release and depletion of l-arginine and determine if arginase inhibition preserves l-arginine and improves pulmonary hemodynamics during PE. Experimental PE was induced in male Sprague-Dawley rats by infusing 25μm microspheres (1.8million/100gbodywt) in the jugular vein, producing moderate pulmonary hypertension. Pulmonary vascular resistance was estimated from the quotient of the right ventricular peak systolic pressure/cardiac output. Arterial plasma hemoglobin (ELISA), arginase activity (colorimetric assay) and l-arginine (high performance liquid chromatography) were determined. Arginase activity was inhibited by infusion of N-omega-hydroxy-nor-l-arginine (nor-NOHA, 400mg/kgbodywt, i.v.). Values are means±s.e. Five hours of PE caused red blood cell hemolysis (15-fold increase in plasma hemoglobin) and release of arginase activity (2.7-fold increase). Plasma l-arginine concentration decreased significantly from 250±20.6 to 118±6.0μmol/L (Control vs. PE) and estimated pulmonary vascular resistance increased 3-fold. Treatment with nor-NOHA prevented the depletion of plasma l-arginine (229±15μmol/L) and reduced the rise in pulmonary vascular resistance by 40%. In conclusion, experimental PE causes hemolysis, release of arginase activity, depletion of plasma l-arginine and increased estimated pulmonary vascular resistance. Inhibition of arginase activity preserves plasma l-arginine levels and improves estimated resistance, suggesting that the release of arginase during hemolysis contributes to the rise in estimated pulmonary resistance during experimental PE.

Original languageEnglish (US)
Pages (from-to)48-54
Number of pages7
JournalPulmonary Pharmacology and Therapeutics
Volume25
Issue number1
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Keywords

  • Arginase
  • Arginine
  • Hemolysis
  • Pulmonary embolism
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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