PRODUCTION OF PULMONARY VASODILATION BY TOLAZOLINE, INDEPENDENT OF NITRIC-OXIDE PRODUCTION IN NEONATAL LAMBS

Objective: To determine whether tolazoline reduces pulmonary vascular resistance (PVR) by means of endogenous nitric oxide production. Desig n: Thirty newborn lambs (2 to 7 days of age) were anesthetized with pe ntobarbital, and their lungs were ventilated through an endotracheal t ube. Intravascular catheters were placed in the left ventricle, descen ding aorta, right atrium, and pulmonary artery for continuous monitori ng of intravascular pressures. Cardiac output was measured with radiol abeled microspheres. Arterial carbon dioxide pressure and pH were main tained in a normal range throughout the experiments, Animals were rand omly assigned to the following groups: group 1, lungs ventilated with a hypoxic gas mixture and administered tolazoline; group 2, given N-om ega-nitro-L-arginine (L-NA) (5 mg/min intravenously for 60 minutes) an d tolazoline; group 3, given L-NA with hypoxia and tolazoline. Acetylc holine (0.5 mu g/kg) was injected into the right atrium to assess pulm onary nitric oxide synthase activity before and after the L-NA infusio n. Data were analyzed by analysis of variance. Results: L-NA inhibited the acetylcholine-induced reduction in mean pulmonary artery pressure (MPAP) by more than 75%. Hypoxia and L-NA increased both MPAP and PVR , Tolazoline produced immediate reductions in both MPAP and PVR in all three groups (group 1, 27% +/- 3% and 50% +/- 5%; group 2, 34% +/- 5% and 50% +/- 6%; and group 3, 31% +/- 4% and 46% +/- 5%, respectively) . Conclusions: These results suggest that tolazoline produces vasodila tion independent of nitric oxide production, Understanding the mechani sm by which tolazoline produces pulmonary vasodilation may provide ins ight into the clinical use of this drug and information regarding othe r potential endogenous mediators of pulmonary vasomotor tone in the ne onate.