Nitric oxide decreases lung liquid production via guanosine 3',5'-cyclic monophosphate

Nitric oxide decreases lung liquid production via guanosine 3',5'-cyclic monophosphate. Am J Physiol Lung Cell Mol Physiol 280: L923-L929, 2001.--We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid production ([J.sub.v]) in chronically instrumented fetal sheep. Forty-five studies were done in which [J.sub.v] was measured by a tracer dilution technique. Left pulmonary arterial flow ([Q.sub.lpa]) was measured by a Doppler flow probe. There were two series of experiments. In the first, we gave 8-bromo-cGMP, a cGMP analog, by either the pulmonary vascular or intraluminal route; in the second, we used agents to inhibit or enhance endogenous cGMP activity. When infused directly into the pulmonary circulation, 8-bromo-cGMP significantly increased [Q.sub.lpa] but had no effect on [J.sub.v]. Conversely, when instilled into the lung liquid, 8-bromo-cGMP had no effect on [Q.sub.lpa] but significantly reduced [J.sub.v]. Inhibition of guanylate cyclase activity with methylene blue totally blocked, whereas phosphodiesterase inhibition with Zaprinast significantly enhanced, the effect of instilled NO on [J.sub.v]. Thus the reduction in lung liquid caused by NO appears to be mediated by cGMP, perhaps through a direct effect on the pulmonary epithelium. pulmonary circulation; guanylate cyclase; birth transition; fetus