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

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• 作者：John A. Watts ; ^{jwatts@carolinas.org} ; Michael A. Gellar ; Mary-Beth K. Fulkerson ; Sudeep K. Das¹ ; Jeffrey A. Kline
• 关键词：Pulmonary embolism ; Hemolysis ; Arginase ; Arginine ; Pulmonary hypertension
• 刊名：Pulmonary Pharmacology & Therapeutics
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：25
• 期：1
• 页码：48-54
• 全文大小：532 K

文摘

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?¦Ìm 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?¡À?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?¡À?20.6 to 118?¡À?6.0?¦Ìmol/L (Control vs. PE) and estimated pulmonary vascular resistance increased 3-fold. Treatment with nor-NOHA prevented the depletion of plasma l-arginine (229?¡À?15?¦Ìmol/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.