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Am J Physiol Heart Circ Physiol 285: H1730-H1737, 2003; doi:10.1152/ajpheart.00938.2002
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Nitric oxide and endothelin in oxygen-dependent regulation of vascular tone of human umbilical vein

Eva Mildenberger,1 Beatrix Biesel,1 Günter Siegel,2 and Hans T. Versmold1

1Department of Pediatrics, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin; and 2Biophysical Research Group, Institute of Physiology, Freie Universität Berlin, 14195 Berlin, Germany

Submitted 30 October 2002 ; accepted in final form 6 June 2003

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 [104 M N{omega}-nitro-L-arginine methyl ester (L-NAME)], ETA receptor blockade (105 M BQ-123), or ETB receptor blockade (107 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.

membrane potential; endothelium; nitric oxide synthase inhibition; endothelin receptor antagonism



Address for reprint requests and other correspondence: E. Mildenberger, Kinderklinik, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany (E-mail: eva.mildenberger{at}medizin.fu-berlin.de).




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