Nitric oxide synthase isoform expression in the developing lung epithelium

Nitric oxide (NO), generated by NO synthase (NOS), is an important mediator of physiological processes in the airway and lung parenchyma, and there is evidence that the pulmonary expression of the endothelial isoform of NOS ( eNOS) is developmentally regulated. The purpose of the present study was to delineate the cellular distribution of expression of eNOS in the developin g respiratory epithelium and to compare it with inducible (iNOS) and neuron al (nNOS) NOS. Immunohistochemistry was performed on fetal (1.25-135 days g estation, term 144 days), newborn (2-4 wk), and maternal sheep lungs. In fe tal lung, eNOS expression was evident in bronchial and proximal bronchiolar epithelia but was absent in terminal and respiratory bronchioles and alveo lar epithelium. Similar to eNOS, iNOS was detected in bronchial and proxima l bronchiolar epithelia but not ill alveolar epithelium. However, iNOS was also detected in terminal and respiratory bronchioles. nNOS was found in ep ithelium at all levels including the alveolar wall. iNOS and nNOS were also detected in airway and vascular smooth muscle. The cellular distribution o f all three isoforms was similar in fetal, newborn, and adult lungs. Findin gs in the epithelium were confirmed by isoform-specific reverse transcripti on-polymerase chain reaction assays and NADPH diaphorase histochemistry. Th us the three NOS isoforms are commonly expressed in proximal lung epitheliu m and are differentially expressed in distal lung epithelium. All three iso forms may be important sources of epithelium-derived NO throughout lung dev elopment.