Kodama T, Marmon L M, Vargas R, Farhat M, Hoy G R, Ramwell P W
Department of Surgery, Georgetown University School of Medicine, Washington, DC 20007.
J Surg Res. 1995 Feb;58(2):227-32. doi: 10.1006/jsre.1995.1035.
Locally produced eicosanoids and endothelium-derived factors are believed to be the mediators of vascular tone of various vascular beds including the mesentery. Using a small vessel isometric myograph which allows direct measurement of microvascular reactivity, the interaction of eicosanoids and endothelium-derived relaxing factor (EDRF) in regulating vascular tone of mesenteric microcirculation of the rat was characterized. The microvascular response to various vasoactive agents before and after inhibition of prostacyclin production with indomethacin (INDO, 5 microM) and inhibition of EDRF synthesis with N omega-nitro-L-arginine methyl ester (L-NAME, 50 microM) was compared. Analysis of dose-response curves for prostaglandin F2 alpha (PGF2 alpha), U46619, a stable thromboxane analog, and norepinephrine (NE) after pretreatment with INDO demonstrated that inhibition of endogenous eicosanoids significantly attenuated the vasoconstrictor response to PGF2 alpha and U46619 but not to NE. Inhibition of EDRF synthesis with L-NAME potentiated the vasoconstrictor response to PGF2 alpha, U46619, and NE. These results suggest that EDRF acts as the primary mediator of vasodilator tone in the mesenteric microcirculation rather than vasodilator cyclooxygenase products such as prostacyclin. It also appears that the vasoconstrictor action of PGF2 alpha and U46619 may be mediated by a release of an endogenous indomethacin-sensitive factor.
局部产生的类二十烷酸和内皮衍生因子被认为是包括肠系膜在内的各种血管床血管张力的介质。使用一种能够直接测量微血管反应性的小血管等长肌张力测定仪，对类二十烷酸与内皮衍生舒张因子（EDRF）在调节大鼠肠系膜微循环血管张力中的相互作用进行了表征。比较了用吲哚美辛（INDO，5微摩尔）抑制前列环素生成以及用Nω-硝基-L-精氨酸甲酯（L-NAME，50微摩尔）抑制EDRF合成前后，微血管对各种血管活性药物的反应。在用INDO预处理后，对前列腺素F2α（PGF2α）、稳定的血栓素类似物U46619和去甲肾上腺素（NE）的剂量-反应曲线分析表明，抑制内源性类二十烷酸可显著减弱对PGF2α和U46619的血管收缩反应，但对NE无此作用。用L-NAME抑制EDRF合成可增强对PGF2α、U46619和NE的血管收缩反应。这些结果表明，EDRF在肠系膜微循环中作为血管舒张张力的主要介质，而非血管舒张性环氧化酶产物如前列环素。此外，PGF2α和U46619的血管收缩作用可能由一种内源性吲哚美辛敏感因子的释放介导。
