Arginase Expression and Activity in Rat Pulmonary Artery are Developmentally Regulated and Highest During Fetal Life

Arginases compete with the nitric oxide synthases for L‐arginine as common substrate. Pathological conditions where arginase activity is increased are associated with reduced L‐arginine availability, decreased nitric oxide production and subsequently impaired smooth muscle relaxation. The developmental patterns of arginases I and II expression in the lung have not been previously evaluated and were the focus of this study. The lung expression of both arginase isoforms, as well as the pulmonary arterial arginase activity was measured in near term fetal, newborn (3 days) and adult rat tissue. In addition, we evaluated the intrapulmonary force generation in the absence and presence of the arginase inhibitor nor‐NOHA. Results: Lung arginase I and II expression, as well as pulmonary artery total arginase activity decreased with age and were lowest in the adult (Figure; ∗P<0.05). Following in vitro incubation with nor‐NOHA, thromboxane A 2 analogue pulmonary arterial force generation was significantly reduced in the fetus and newborn (P<0.01, respectively), but not adult rats. In conclusion, arginase I and II are 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 nitric oxide production prenatally may in part be dependent on increased arginase expression and/or activity.