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 Kline

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 2012
Externally publishedYes

Fingerprint

Arginase
Pulmonary Embolism
Blood Vessels
Arginine
Plasmas
Lung
Hemolysis
Vascular Resistance
Hemoglobins
Blood
Erythrocytes
Cells
Jugular Veins
Hemodynamics
High performance liquid chromatography
Microspheres
Pulmonary Hypertension
Cardiac Output
Sprague Dawley Rats
Rats

Keywords

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

ASJC Scopus subject areas

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

Cite this

Arginase depletes plasma l-arginine and decreases pulmonary vascular reserve during experimental pulmonary embolism. / Watts, John A.; Gellar, Michael A.; Fulkerson, Mary Beth K; Das, Sudeep K.; Kline, Jeffrey.

In: Pulmonary Pharmacology and Therapeutics, Vol. 25, No. 1, 02.2012, p. 48-54.

Research output: Contribution to journalArticle

Watts, John A. ; Gellar, Michael A. ; Fulkerson, Mary Beth K ; Das, Sudeep K. ; Kline, Jeffrey. / Arginase depletes plasma l-arginine and decreases pulmonary vascular reserve during experimental pulmonary embolism. In: Pulmonary Pharmacology and Therapeutics. 2012 ; Vol. 25, No. 1. pp. 48-54.
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