ENDOTHELIUM-DERIVED NITRIC-OXIDE PLAYS A LARGER ROLE IN PULMONARY VEINS THAN IN ARTERIES OF NEWBORN LAMBS

In perinatal lungs, veins contribute substantially to total pulmonary vascular resistance. The present study was designed to determine the r ole of endothelium-derived nitric oxide (EDNO) in modulating the respo nsiveness of pulmonary veins and arteries in newborn lambs. Fourth-ord er pulmonary arterial and venous rings of newborn lambs were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solut ion (95% O-2/5% CO2, 37 degrees C), and their isometric force was meas ured. Nitro-L-arginine had no effect on the resting tension of pulmona ry arteries but caused an endothelium-dependent contraction of pulmona ry veins. During contraction to endothelin-1 or U46619, acetylcholine, bradykinin, and calcium ionophore A23187 induced larger endothelium-d ependent relaxation in pulmonary veins than in arteries. The endotheli um-dependent relaxation of pulmonary vessels was abolished by nitro-L- arginine. In vessels without endothelium, nitric oxide induced signifi cantly greater relaxation in pulmonary veins than in arteries. All ves sels relaxed similarly to 8-bromo-cGMP. Radioimmunoassay showed that t he basal level of intracellular cGMP of pulmonary veins with endotheli um was higher than that of arteries with endothelium. Acetylcholine, b radykinin, and calcium ionophore A23187 induced a significantly larger endothelium-dependent increase in the intracellular content of cGMP i n pulmonary veins than in arteries. In vessels without endothelium, ni tric oxide induced a larger increase in cGMP content in pulmonary vein s than in arteries. The present study suggests that EDNO may play a la rger role in modulation of pulmonary venous than arterial reactivity, which may be mainly due to a difference in the activity of soluble gua nylate cyclase in vascular smooth muscle.