Nitric oxide decreases lung liquid production via guanosine 3',5'-cyclic monophosphate.
We studied the role of cGMP in nitric oxide (NO)-induced changes in lung liquid 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 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(lpa) but had no effect on J(v). Conversely, when instilled into the lung liquid, 8-bromo-cGMP had no effect on Q(lpa) but significantly reduced J(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(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.
Cummings
J J
JJ
Department of Pediatrics, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA. cummingsj@mail.ecu.edu
Wang
H
H
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000008:administration & dosage; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D004333:Drug Administration Routes; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005333:Fetus; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008751:Methylene Blue / Q000008:administration & dosage; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects; D011688:Purinones / Q000008:administration & dosage; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D011688:Purinones; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase; C011145:zaprinast; D006152:Cyclic GMP; D008751:Methylene Blue