Developmental changes in arginase expression and activity in the lung.
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.
Belik
Jaques
J
Department of Pediatrics, Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, and University of Toronto, 555 University Ave., Toronto, Ontario, M5G 1X8 Canada. jaques.belik@sickkids.ca
Shehnaz
Darakhshanda
D
Pan
Jingyi
J
Grasemann
Hartmut
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008168:Lung / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development*; D011247:Pregnancy; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology; D051381:Rats
C404735:N(omega)-hydroxynorarginine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; C113162:Arg2 protein, rat; D001119:Arginase