ENDOTHELIUM-DEPENDENT RELAXATION AND CYCLIC-GMP ACCUMULATION IN RABBIT PULMONARY-ARTERY ARE SELECTIVELY IMPAIRED BY MODERATE HYPOXIA
ENDOTHELIUM-DEPENDENT RELAXATION AND CYCLIC-GMP ACCUMULATION IN RABBIT PULMONARY-ARTERY ARE SELECTIVELY IMPAIRED BY MODERATE HYPOXIA
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DOI：
10.1161/01.res.65.6.1508
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发表时间：
1989-12-01
影响因子：
20.1
通讯作者：
PEACH, MJ
中科院分区：
文献类型：
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作者：
JOHNS, RA;LINDEN, JM;PEACH, MJ
在兔第一支肺动脉的去氧肾上腺素预收缩的隔离环中研究了缺氧对内皮依赖性和内皮非依赖性血管舒张的影响。在吲哚美辛（2.8×1mmHg）存在下，在暴露于缺氧（Po2=42±1mmHg）之前、期间和之后，获得对内皮依赖性扩张剂醋甲胆碱、ATP和钙离子载体（A23187）以及内皮非依赖性扩张剂硝普钠和异丙肾上腺素的浓度依赖性松弛反应。 10-5 M）。这种中等程度的缺氧抑制（p < 0.05）内皮依赖性舒张反应，但不抑制内皮非依赖性舒张反应，且不会产生不可逆的血管损伤。在平行实验中，在存在和不存在缺氧的情况下，测量了对上述血管扩张剂的最大剂量的响应的肺血管环中环鸟苷酸的积累。缺氧会抑制内皮依赖性扩张剂（乙酰甲胆碱、ATP 和 A23187）引起的环 GMP 积累（p < 0.05），而内皮非依赖性扩张剂硝普钠引起的环 GMP 积累则不会受到抑制。当去氧肾上腺素预收缩的血管在没有血管扩张剂的情况下暴露于缺氧时，会发生小幅短暂的张力增加，在内皮完整的血管中比内皮剥脱的血管更大（分别为 0.70 .+-. 0.12 与 0.09 .+-. 0.03 g；p < 0.01）。在血红蛋白（1×10-6M；p<0.01）、亚甲蓝（1×10-7M；p<0.01）和氢醌（1×10-6M；p<0.01）存在的情况下，张力的增加在完整内皮环中减少，但在内皮剥脱环中不减少。缺氧还降低了内皮完整去氧肾上腺素预收缩环中的基础环 GMP 含量（1.23 .+-. 0.22 与 0.79 .+-. 0.19 pmol/mg 蛋白质；p < 0.05）。这些数据表明，这些大肺动脉中缺氧引起的短暂血管收缩部分是由于基础 EDRF 产生的抑制。观察到的药理学反应表明，缺氧诱导的内皮依赖性扩张抑制的位点在内皮细胞中受体介导的事件的远端，并且在血管平滑肌中鸟苷酸环化酶的激活的近端。
The effect of hypoxia on endothelium-dependent and endothelium-independent vasodilation was studied in phenylephrine-precontracted, isolated rings of rabbit first-branch pulmonary artery. Concentration-dependent relaxation responses to the endothelium-dependent dilators methacholine, ATP, and the calcium ionophore (A23187) as well as the endothelium-independent dilators sodium nitroprusside and isoproterenol were obtained before, during, and after exposure to hypoxia (Po2 = 42 .+-. 1 mm Hg) in the presence of indomethacin (2.8 .times. 10-5 M). This moderate degree of hypoxia inhibited (p < 0.05) endothelium-dependent but not endothelium-independent relaxation responses without producing irreversible vascular damage. In parallel experiments, cyclic GMP accumulation in pulmonary vascular rings in response to maximal doses of the above vasodilators was measured in the presence and absence of hypoxia. Cyclic GMP accumulation in response to endothelium-dependent dilators (methacholine, ATP, and A23187) was inhibited (p < 0.05) by hypoxia while cyclic GMP accumulation in response to the endothelium-independent dilator sodium nitroprusside was not. When phenylephrine precontracted vessels were exposed to hypoxia in the absence of vasodilators, a small, transient increase in tension occurred, which was greater in endothelium-intact than in endothelium denuded vessels (0.70 .+-. 0.12 vs. 0.09 .+-. 0.03 g, respectively; p < 0.01). This increase in tension was reduced in the presence of hemoglobin (1 .times. 10-6 M; p < 0.01), methylene blue (1 .times. 10-7 M; p < 0.01), and hydroquinone (1 .times. 10-6 M; p < 0.01) in endothelium-intact but not in endothelium denuded rings. Hypoxia also reduced basal cyclic GMP content in endothelium-intact phenylephrine-precontracted rings (1.23 .+-. 0.22 vs. 0.79 .+-. 0.19 pmol/mg protein; p < 0.05). These data suggest that the transient vasoconstriction induced by hypoxia in these large pulmonary arteries is due partially to the inhibition of basal EDRF production. The observed pharmacological responses imply that the site of hypoxia-induced inhibition of endothelium-dependent dilation is distal to receptor-mediated events in the endothelial cell and proximal to activation of guanylate cyclase in the vascular smooth muscle.