We have previously found that H2-receptor blockade in newborn lungs causes an increase in baseline normoxic pulmonary arterial pressure. Increased pulmonary arterial pressure is associated with decreased nitric oxide (NO) production. We tested the hypothesis that H2-receptor blockade causes a decrease in NO production in newborn piglet lungs under normoxic conditions. Lungs from newborn piglets were isolated and perfused with a Krebs-Ringers bicarbonate buffer solution containing 5% dextran (100 ml/kg/min). After a stabilization period, cimetidine (0.007 to 7.0 mM) was added to the perfusate. Exhaled NO was measured by a chemiluminescence analyzer during constant tidal ventilation with a normoxic gas mixture. The graph shows that cimetidine caused a decrease in exhaled NO (eNO) expressed as a percent change from baseline. This suggests that cimetidine decreased NO production in these lungs. Therefore in neonatal conditions associated with pulmonary hypertension, concomitant usage of H2-antagonists may exacerbate already elevated pulmonary arterial pressures.Figure

figure 1

Funded by the March of Dimes, the AHA and the Dept. of VA.