Pulmonary neuroendocrine cells in nitrofen-induced diaphragmatic hernia and the effect of prenatal glucocorticoids

The high mortality associated with congenital diaphragmatic hernia (CDH) is due to pulmonary hypoplasia and hypertension, structural and functional ab normalities which can to some extent be ameliorated by prenatal administrat ion of glucocorticoids. Tn the hypoplastic, hypertensive lungs of neonatal rats in which CDH has been induced by nitrofen, those pulmonary neuroendocr ine cells (PNCs) containing calcitonin gene-related peptide (CGRP) increase in number, and it has been suggested that this might be due to inhibition of secretion of the peptide, the consequent decrease in its vasodilatory ef fects contributing to the hypertension. Whether this increase affects the e ntire population of PNCs, however, and how these cells are affected by admi nistration of prenatal glucocorticoids, is unknown. As revealed by immunola belling for protein gene product (PCP) 9.5, a general marker of NCs and exp ressed per cm(2) tissue section, the total PNC population in rats with nitr ofen-induced CDH was significantly greater than in controls receiving only olive oil (672 vs 375/cm(2), P = 0.03) and was further increased (824 per c m(2)) in animals treated prenatally with dexamethasone (n = 8 in all groups ). The increase in the total PNC population in rats with CDH is similar in magnitude to that described for the CGRP-containing subpopulation. Since th e major role of the products of PNCs is now thought to be the regulation of development of pulmonary tissues and their response to injury, it is proba ble that the expansion of their population in the abnormal lungs associated with CDH is an adaptive response to pulmonary maldevelopment, a response p ossibly augmented by exogenous corticosteroids.