title: Endothelium-derived nitric oxide plays a larger role in pulmonary veins than in arteries of newborn lambs.
abstract: In perinatal lungs, veins contribute substantially to total pulmonary vascular resistance. The present study was designed to determine the role of endothelium-derived nitric oxide (EDNO) in modulating the responsiveness of pulmonary veins and arteries in newborn lambs. Fourth-order pulmonary arterial and venous rings of newborn lambs were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2/5% CO2, 37 degrees C), and their isometric force was measured. Nitro-L-arginine had no effect on the resting tension of pulmonary arteries but caused an endothelium-dependent contraction of pulmonary veins. During contraction to endothelin-1 or U46619, acetylcholine, bradykinin, and calcium ionophore A23187 induced larger endothelium-dependent relaxation in pulmonary veins than in arteries. The endothelium-dependent relaxation of pulmonary vessels was abolished by nitro-L-arginine. In vessels without endothelium, nitric oxide induced significantly greater relaxation in pulmonary veins than in arteries. All vessels relaxed similarly to 8-bromo-cGMP. Radioimmunoassay showed that the basal level of intracellular cGMP of pulmonary veins with endothelium was higher than that of arteries with endothelium. Acetylcholine, bradykinin, and calcium ionophore A23187 induced a significantly larger endothelium-dependent increase in the intracellular content of cGMP in pulmonary veins than in arteries. In vessels without endothelium, nitric oxide induced a larger increase in cGMP content in pulmonary veins than in arteries. The present study suggests that EDNO may play a larger role in modulation of pulmonary venous than arterial reactivity, which may be mainly due to a difference in the activity of soluble guanylate cyclase in vascular smooth muscle.
authors.affiliation: Department of Pediatrics, Harbor-UCLA Medical Center, School of Medicine, Torrance.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.forename: H
authors.initials: H
authors.lastname: Zhou
authors.forename: J U
authors.initials: JU
authors.lastname: Raj
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011667:Pulmonary Veins / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011863:Radioimmunoassay; D012756:Sheep; D014655:Vascular Resistance
chemical_list: D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin