ROLE OF ENDOTHELIUM IN THE MAINTENANCE OF LOW PULMONARY VASCULAR TONEIN NORMAL-CHILDREN

Background Resting vascular tone is low in the normal pulmonary circul ation, and experimental studies have suggested that this may be due to the continuous release of endothelium-derived nitric oxide (NO), a lo cally acting vasodilator. We have investigated whether NO contributes to the normal control of pulmonary vascular tone and resistance in chi ldren. Methods and Results We studied the hemodynamic effects of N-G-m onomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis, o n the pulmonary circulation of six children 2 to 17 years old (mean, 9 years) with congenital heart disease but normal pulmonary blood flow, pressure, and resistance (all had isolated left heart obstructive les ions). The diameter of a segmental pulmonary artery and pulmonary bloo d flow velocity were measured by quantitative angiography and intraart erial Doppler catheters. There was a consistent, dose-dependent fall i n pulmonary blood flow velocity in response to three increasing doses of L-NMMA (compared with baseline, flow velocity fell to 75+/-7%, 62+/ -8%, and 40+/-10%, P<.01). Flow velocity returned to control values wi th subsequent infusion of L-arginine, the substrate for NO. Thereafter , acetylcholine, an endothelium-dependent dilator, produced an increas e in flow velocity (56+/-10% greater than baseline, P<.01). Arterial d iameter was unchanged during L-NMMA and L-arginine infusions, indicati ng that the major effect of each agent is to alter vascular tone dista l to the segmental pulmonary arteries. Conclusions The dilator action of endothelium-derived NO contributes to the maintenance of low restin g pulmonary tone in nounal children. Impairment of NO production may c ontribute to the elevated pulmonary vascular resistance that complicat es some cases of congenital heart disease.