Reduction in Lung Liquid Production Caused by Nitric Oxide is Blocked by Methylene Blue. † 1484

We have previously shown that nitric oxide (NO), an important mediator of pulmonary vasodilation at birth, reduces lung liquid production (Pediatr Res 1994; 329A) and that this effect is mimicked by instilling cGMP directly into the fetal lung liquid (Pediatr Res 1997). To further define the role of cGMP in nitric oxide induced reduction in lung liquid, we studied the effects of methylene blue, which inhibits the activation of guanylate cyclase by nitric oxide, on lung liquid production and pulmonary hemodynamics in six chronically instrumented fetal sheep at an average gestational age of 130 ± 4 d. Net lung luminal liquid production (J_v) was measured by plotting the change in lung luminal liquid concentration of radiolabelled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. J_v was measured during a 1-2 h baseline, then for 2-3 h following instillation of methylene blue (3 mg), then for 2-3 h following instillation of methylene blue and a 10% saturated nitric oxide solution (5 ml). Results were: (Qp = left pulmonary blood flow; PA=pulmonary artery; CA=carotid artery; LA = left atrium; HR = heart rate):Table Control (saline) instillations (n=8) caused no significant change in any variable. Previous studies using the same dose of nitric oxide resulted in a 75% reduction in Jv. Thus, methylene blue totally blocked the effect of nitric oxide on Jv, supporting the notion that nitric oxide reduces Jv by stimulating guanylate cyclase.

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Funded by AHA Grant-in-Aid #94-317 and the J.H. Cummings Foundation