Mildenberger Eva, Biesel Beatrix, Siegel Günter, Versmold Hans T
Department of Pediatrics, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1730-7. doi: 10.1152/ajpheart.00938.2002.
We investigated the possible contribution of nitric oxide (NO) and endothelin (ET) to oxygen-dependent regulation of human umbilical vein vascular tone by simultaneous registration of intracellular membrane potential and isometric tension of vessel strips with and without NO synthase inhibition [10-4 M N omega-nitro-L-arginine methyl ester (L-NAME)], ETA receptor blockade (10(-5) M BQ-123), or ETB receptor blockade (10(-7) M BQ-788) at Po2 values in the bath solution between 5 and 104 mmHg. Increasing PO2 above the physiological intrauterine range resulted in depolarization and an increase of isometric tension, whereas lowering PO2 resulted in hyperpolarization and a decrease in isometric tension. Removal of the endothelium reversed these effects. At PO2 values below 39 mmHg, intact preparations treated with either L-NAME, BQ-788, or BQ-123 were more depolarized than controls. In the case of treatment with L-NAME or BQ-123, this was accompanied by an increase in isometric tension. We conclude that it is NO that mediates the hypoxic hyperpolarization and vasodilatation of the human umbilical vein and that ET, via activation of ETB1 receptors on endothelial cells, contributes to this effect.
我们通过在浴液中氧分压（Po2）值介于5至104 mmHg之间时，同时记录细胞内膜电位以及血管条的等长张力，研究了一氧化氮（NO）和内皮素（ET）对人脐静脉血管张力氧依赖性调节的可能作用，其中血管条分别有无一氧化氮合酶抑制（10-4 M Nω-硝基-L-精氨酸甲酯（L-NAME））、ETA受体阻断（10(-5) M BQ-123）或ETB受体阻断（10(-7) M BQ-788）。将Po2提高至生理子宫内范围以上会导致去极化和等长张力增加，而降低Po2则会导致超极化和等长张力降低。去除内皮会逆转这些效应。在Po2值低于39 mmHg时，用L-NAME、BQ-788或BQ-123处理的完整标本比对照更去极化。在用L-NAME或BQ-123处理的情况下，这伴随着等长张力增加。我们得出结论，是NO介导了人脐静脉的缺氧超极化和血管舒张，并且ET通过激活内皮细胞上的ETB1受体促成了这一效应。
