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 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.
Gao
Y
Y
Department of Pediatrics, Harbor-UCLA Medical Center, School of Medicine, Torrance.
Zhou
H
H
Raj
J U
JU
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
D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin