Gruetter C A, Lemke S M, Valentovic M A, Szarek J L
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Eur J Pharmacol. 1994 May 23;257(3):275-83. doi: 10.1016/0014-2999(94)90139-2.
This study was initiated to test the hypothesis that histamine can act as an endothelium-derived contracting factor in bovine isolated intrapulmonary vein. The effects of calcium ionophore, calcimycin (A23187), on isometric tension were compared in unstimulated rings of intrapulmonary vein with and without endothelium. A23187 (0.1-10 microM) induced concentration-related contraction when endothelium was present. Destruction of endothelium markedly inhibited A23187-induced contraction. Methylene blue, hemoglobin or NG-methyl-L-arginine significantly enhanced A23187-induced contraction only in venous rings with endothelium consistent with attenuation of the contraction by the concomitant release of endothelium-derived relaxing factor (nitric oxide) [EDRF(NO)]. Histamine H1 receptor antagonists inhibited, and iproniazid enhanced, contraction elicited by A23187. A23187 induced release of greater amounts of histamine from venous rings with than without endothelium. A23187-induced contraction was not mimicked by the mast cell activator, compound 48/80, and was not inhibited by preexposure to compound 48/80 or in the presence of cromolyn or doxantrazole. A23187-induced contraction was not inhibited by pretreatment with indomethacin, phentolamine, lipoxygenase inhibitors or superoxide dismutase. The results indicate that A23187 induces endothelium-dependent contraction in bovine intrapulmonary vein and support histamine as one major mediator involved. The association of destruction of endothelium with an inhibition of both A23187-induced contraction and histamine release is consistent with the endothelium as a source for histamine which can exert a local vasoconstrictor effect in bovine intrapulmonary vein.
开展本研究是为了验证组胺可作为牛离体肺内静脉中一种内皮源性收缩因子的假说。在有无内皮的肺内静脉未受刺激的环中，比较了钙离子载体A23187对肺内静脉等长张力的影响。当存在内皮时，A23187（0.1 - 10 μM）可诱导浓度依赖性收缩。内皮破坏显著抑制了A23187诱导的收缩。亚甲蓝、血红蛋白或NG-甲基-L-精氨酸仅在有内皮的静脉环中显著增强了A23187诱导的收缩，这与内皮源性舒张因子（一氧化氮）[EDRF(NO)]的释放导致收缩减弱一致。组胺H1受体拮抗剂抑制了A23187引发的收缩，而异烟酰异丙肼则增强了该收缩。与无内皮的静脉环相比，A23187从有内皮的静脉环中诱导释放出更多的组胺。肥大细胞激活剂化合物48/80不能模拟A23187诱导的收缩，预先暴露于化合物48/80或在存在色甘酸钠或多沙唑嗪的情况下，A23187诱导的收缩也不受抑制。吲哚美辛、酚妥拉明、脂氧合酶抑制剂或超氧化物歧化酶预处理均不能抑制A23187诱导的收缩。结果表明，A23187在牛肺内静脉中诱导内皮依赖性收缩，并支持组胺作为其中一个主要参与的介质。内皮破坏与A23187诱导的收缩和组胺释放均受抑制相关，这与内皮作为组胺来源一致，组胺可在牛肺内静脉中发挥局部血管收缩作用。
