. Nitric oxide and endothelin in oxygen-dependent regulation of vascular tone of human umbilical vein. Am J Physiol Heart Circ Physiol 285: H1730-H1737, 2003; 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
Ϫ4M N -nitro-L-arginine methyl ester (L-NAME)], ETA receptor blockade (10 Ϫ5 M BQ-123), or ETB receptor blockade (10 Ϫ7 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 BLOOD FLOW FROM THE PLACENTA to the fetus is determined by the difference between fetal aortic blood pressure and umbilical vein blood pressure, which in turn depends on umbilical vein vascular tone. The contribution of umbilical vein vascular tone to the regulation of umbilical blood flow had been regarded as negligible, because the umbilical vein was thought to operate at maximal vasodilatation already at resting conditions (6). However, a recent study (15) from our laboratory has revealed that the human umbilical vein is far from being a passive conduit, but is able to adjust its vascular tone in response to changes in local PO 2 . In particular, we found endothelium-dependent vasodilatation at hypoxia.Because the human umbilical vein is thought to lack autonomic innervation (4, 21), local mechanisms of regulation of vascular tone may be of particular relevance. Besides prostanoids, endothelial nitric oxide (NO) and endothelin (ET) are the most important locally released factors regulating vascular tone. There is a continuous basal release of NO from the vascular endothelium, and increased release of NO contributes to endothelium-dependent vasodilatation in response to various stimuli (16). We therefore asked whether NO contributes to oxygen-dependent regulation of human umbilical vein vascular tone and studied the effects of inhibition of NO synthesis by N -nitro-L-arginine methyl ester (L-NAME) on membrane potential and isometric tension of intact human umbilical vein preparations at different local PO 2 values.There is also evidence for a basal re...