Gao Y, Tolsa J F, Raj J U
Department of Pediatrics, Harbor-UCLA Medical Center, University of California, Los Angeles School of Medicine, Torrance 90509, USA.
Pediatr Res. 1998 Nov;44(5):723-9. doi: 10.1203/00006450-199811000-00015.
Endothelium-derived nitric oxide (EDNO) plays a pivotal role in regulating pulmonary circulation. To determine whether there is a heterogeneity in EDNO-mediated responses of different sized pulmonary vessels, we studied small and large isolated pulmonary arteries of newborn lambs (diameter, 0.4-0.7 and 1.5-2.5 mm, respectively). The isometric tension of vessel rings were recorded while suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2-5% CO2, 37 degrees C). In vessels preconstricted with norepinephrine, acetylcholine and bradykinin induced a greater relaxation of small pulmonary arteries than of large pulmonary arteries. Acetylcholine, bradykinin, and nitric oxide also induced a greater increase in cGMP content in small arteries than in large ones. The responses to acetylcholine and bradykinin were endothelium-dependent and inhibited by nitro-L-arginine, an inhibitor of nitric oxide synthase. In vessels without endothelium, the response to nitric oxide was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase. The activity of soluble guanylyl cyclase of small arteries was greater than that of large arteries under basal conditions and after stimulation with S-nitroso-N-acetylpenicillamine, a nitric oxide donor. These results demonstrate that heterogeneity exists in EDNO-mediated relaxation of small and large pulmonary arteries in newborn lambs. A difference in the soluble guanylate cyclase activity of vascular smooth muscle may have contributed to this phenomenon.
内皮衍生的一氧化氮（EDNO）在调节肺循环中起关键作用。为了确定不同大小的肺血管对EDNO介导的反应是否存在异质性，我们研究了新生羔羊的小和大的离体肺动脉（直径分别为0.4 - 0.7和1.5 - 2.5毫米）。将血管环悬挂在充满改良的克雷布斯 - 林格碳酸氢盐溶液（95% O₂ - 5% CO₂，37℃）的器官浴槽中记录其等长张力。在用去甲肾上腺素预收缩的血管中，乙酰胆碱和缓激肽诱导小肺动脉的舒张程度大于大肺动脉。乙酰胆碱、缓激肽和一氧化氮也诱导小动脉中cGMP含量的增加大于大动脉。对乙酰胆碱和缓激肽的反应是内皮依赖性的，并被一氧化氮合酶抑制剂硝基 - L - 精氨酸所抑制。在无内皮的血管中，对一氧化氮的反应被可溶性鸟苷酸环化酶抑制剂1H - [1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮所抑制。在基础条件下以及用一氧化氮供体S - 亚硝基 - N - 乙酰青霉胺刺激后，小动脉中可溶性鸟苷酸环化酶的活性大于大动脉。这些结果表明新生羔羊的小和大肺动脉在EDNO介导的舒张方面存在异质性。血管平滑肌中可溶性鸟苷酸环化酶活性的差异可能导致了这一现象。
