Infants with congenital heart lesions that are associated with increased pulmonary blood flow may exhibit altered pulmonary vascular responses to endothelium-dependent agents and develop pulmonary hypertension. Decreased production of the endogenous vasodilator, nitric oxide (NO) could contribute to these alterations. The purpose of this study was to determine the effect of in vivo increased pulmonary blood flow on endothelium-dependent responses and the amount of endothelial nitric oxide synthase (eNOS), the enzyme responsible for basal NO production, in lungs of piglets. Left thoracotamies were performed in newborn piglets at age 5-7 days. An aortic-pulmonary shunt was placed in 4 piglets and 6 other piglets underwent a sham operation (sham). At 5-6 weeks of age, all piglets were anesthetized and catheters placed for determination of pulmonary arterial pressure (Ppa), pulmonary wedge pressure, and cardiac output (CO). Lungs of the piglets were then excised and perfused with blood. While maintaining constant flow, Ppa responses to acetylcholine(10-5 M) were measured. An immunoblot technique was applied to whole lung homogenates. We found that Ppa, CO, and pulmonary vascular resistance(PVR) were greater in the shunted than in the sham piglets (values in shunt vs sham piglets: Ppa was 32.6 ± 0.5 cm H20 vs 14.8 ± 0.5 cm H2O; CO was 368 ± 61 ml/kg/min vs 213 ± 22 ml/kg/min and PVR was.08 ±.01 vs.05 ±.01 cm H2O·ml-1·min·kg). The acetylcholine induced decrease in Ppa was less in isolated lungs of shunted than in sham piglets(8±1% vs 15±1%). As assessed by laser densitometry, eNOS protein amounts did not differ between lung homogenates from shunted as compared to sham piglets. Thus, although pulmonary hypertension developed and endothelium dependent responses were blunted, the amount of eNOS was not decreased in lungs of shunted piglets with a 73% increase in cardiac output. These findings suggest that decreased eNOS is not the mechanism for the altered pulmonary vascular responses or the pulmonary hypertension associated with 5-6 weeks of increased pulmonary blood flow in newborn piglets. Supported by the March of Dimes, Children's Hosp. Foundation and AHA WI Affiliate.
