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

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 25 μm microspheres (1.8 million/100 g body wt) 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, 400 mg/kg body wt, 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 ± 6.0 μmol/L (Control vs. PE) and estimated pulmonary vascular resistance increased 3-fold. Treatment with nor-NOHA prevented the depletion of plasma l -arginine (229 ± 15 μmol/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.