Developmental Changes in Arginase Expression and Activity in the Lung

Am J Physiol Lung Cell Mol Physiol. 2008 Mar;294(3):L498-504. doi: 10.1152/ajplung.00242.2007. Epub 2008 Jan 11.

Abstract

Arginases compete with nitric oxide (NO) synthases for L-arginine as common substrate. Pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation. The developmental patterns of arginase activity and type I and II isoforms expression in the lung have not been previously evaluated. Hypothesizing that lung arginase activity is developmentally regulated and highest in the fetus, we measured the expression of both arginase isoforms and total arginase activity in fetal, newborn, and adult rat lung, pulmonary artery, and bronchial tissue. In addition, intrapulmonary arterial muscle force generation was evaluated in the absence and presence of the arginase inhibitor Nomega-hydroxy-nor-L-arginine (nor-NOHA). Arginase II content, as well as total arginase activity, was highest in fetal rat lung, bronchi, and pulmonary arterial tissue and decreased with age (P<0.05), and its lung cell expression was developmentally regulated. In the presence of nor-NOHA, pulmonary arterial force generation was significantly reduced in fetus and newborn (P<0.01). No significant change in force generation was noted in bronchial tissue following arginase inhibition. In conclusion, arginase II is regulated developmentally, and both expression and activity are maximal during fetal life. We speculate that the maintenance of a high pulmonary vascular resistance and decreased lung NO production prenatally may, in part, be dependent on increased arginase expression and/or activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Animals
  • Arginase / metabolism*
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Bronchi / drug effects
  • Bronchi / physiology
  • Female
  • Gene Expression Regulation, Developmental*
  • Immunohistochemistry
  • Lung / embryology
  • Lung / enzymology*
  • Lung / growth & development*
  • Pregnancy
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / enzymology
  • Rats

Substances

  • N(omega)-hydroxynorarginine
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Arginine
  • Arg2 protein, rat
  • Arginase