Ishikawa S, Tsukada H, Yuasa H, Fukue M, Wei S, Onizuka M, Miyauchi T, Ishikawa T, Mitsui K, Goto K
Department of Surgery, University of Tsukuba, Ibaraki, Japan.
J Appl Physiol (1985). 1992 Jun;72(6):2387-92. doi: 10.1152/jappl.1992.72.6.2387.
We examined the effects of endothelin-1 (ET-1) on pulmonary hemodynamic and transvascular fluid filtration and the conversion of big endothelin-1 (big ET-1), a precursor of ET-1, in isolated perfused rabbit lungs at constant vascular and airway pressures. Furthermore we examined whether ET-1 contributes to cyclooxygenase metabolism. The perfusate flow decreased significantly after bolus administration of 1 or 0.1 nmol of ET-1. Lung weight did not increase throughout the experimental period. Big ET-1- (1 nmol) induced decrease in the flow was slow in developing, although the maximum response was comparable to that induced by the same dose of ET-1. The concentration of bit ET-1 in the perfusate progressively decreased, while that of ET-1 increased in a time-dependent manner. Phosphoramidon, an inhibitor of metalloproteinase, suppressed the pressor effect of big ET-1 (P less than 0.01) and the increase in the concentration of ET-1 in the perfusate (P less than 0.05). The present findings provide the first evidence suggesting that the potent vasocontractile effect of big ET-1 in pulmonary circulation can be attributed to the production of ET-1 by the conversion from big ET-1 in the vascular bed. ET-1-induced perfusate flow changes were not affected by indomethacin, and the concentration of 6-ketoprostaglandin F1 alpha, a metabolite of prostacyclin, did not increase after ET-1 administration.
我们在恒定血管和气道压力下，研究了内皮素 -1（ET -1）对离体灌注兔肺的肺血流动力学、跨血管液体滤过以及ET -1前体大内皮素 -1（big ET -1）转化的影响。此外，我们还研究了ET -1是否参与环氧化酶代谢。静脉注射1或0.1 nmol ET -1后，灌注液流量显著降低。在整个实验期间肺重量未增加。大内皮素 -1（1 nmol）引起的流量降低发展缓慢，尽管最大反应与相同剂量ET -1引起的反应相当。灌注液中big ET -1的浓度逐渐降低，而ET -1的浓度则呈时间依赖性增加。金属蛋白酶抑制剂磷酰胺素抑制了大内皮素 -1的升压作用（P < 0.01）以及灌注液中ET -1浓度的增加（P < 0.05）。本研究结果首次表明，大内皮素 -1在肺循环中的强效血管收缩作用可归因于其在血管床中由big ET -1转化生成ET -1。ET -1引起的灌注液流量变化不受吲哚美辛影响，ET -1给药后前列环素的代谢产物6 -酮前列腺素F1α的浓度未增加。
