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

We studied the role of cGMP in nitric oxide (NO)-induced changes in lung li quid production (J(v)) in chronically instrumented fetal sheep. Forty-five studies were done in which J(v) was measured by a tracer dilution technique . Left pulmonary arterial flow (Q(lpa)) was measured by a Doppler flow prob e. 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 signifi cantly increased Q(lpa) but had no effect on J(v). Conversely, when instill ed into the lung liquid, 8-bromo-cGMP had no effect on Q(lpa) but significa ntly reduced J(v). Inhibition of guanylate cyclase activity with methylene blue totally blocked, whereas phosphodiesterase inhibition with Zaprinast s ignificantly enhanced, the effect of instilled NO on J(v). Thus the reducti on in lung liquid caused by NO appears to be mediated by cGMP, perhaps thro ugh a direct effect on the pulmonary epithelium.