Diaspirin Cross-linked Hemoglobin Does not Alter Isolated Human Umbilical Artery or Vein Tone

Abstract

Diaspirin cross-linked hemoglobin (DCLHb^TM; Baxter Healthcare Corp., Round Lake, IL, USA) is undergoing clinical trials as a blood substitute. Administration of DCLHb is associated with an increase of mean arterial pressure in vivo and contraction of selected adult isolated blood vessels of from certain species in vitro. The mechanisms of these pressor effects may be due to scavenging of the endothelium derived relaxing factor, nitric oxide (NO), by hemoglobin. Unlike adult blood vessels, prostacyclin (PGI₂) rather than EDNO is the important relaxing agent in human umbilical vessels. In this study, we examined if DCLHb had vasoconstrictor effects on isolated human umbilical vessels. Human umbilical veins and arteries were excised, cut into rings and placed in organ chambers filled with 25 ml Krebs-Ringer solution (37°C). 5-hydroxytryptamine (5-HT, 0.01–10 μM) increased the tension of human umbilical arteries (HUA, from 0.4±0.2g to 2.6±0.4g) and veins (HUV, from 0.8±0.4g to 2.5±0.4g) in a dose-dependent manner. DCLHb (0.01–10 μM) did not have a significant effect on HUA and HUV. Substance P (1 μM, via prostanoid synthesis) and nitroglycerin(NG, 1 μM) but not acetylcholine (ACh, 1 μM) caused relaxation of both HUA and HUV. The NO synthase inhibitor L-NA did not have significant effects on HUA and HUV. DCLHb did not alter 5-HT preconstricted tension of HUA and HUV. The basal cGMP contents of HUA and HUV were low. These results support our previous finding that DCLHb-induced vasoconstriction in isolated vessels is dependent primarily on the binding of NO by hemoglobin.