DIASPIRIN CROSS-LINKED HEMOGLOBIN DOES NOT ALTER ISOLATED HUMAN UMBILICAL ARTERY OR VEIN TONE

Diaspirin cross-linked hemoglobin (DCLHb(TM); Baxter Healthcare Corp., Round Lake, LL, USA) is undergoing clinical trials as a blood substit ute. Administration of DCLHb is associated with an increase of mean ar terial pressure in vivo and contraction of selected adult isolated blo od vessels of from certain species in vitro. The mechanisms of these p resser effects may be due to scavenging of the endothelium derived rel axing factor, nitric oxide (NO), by hemoglobin. Unlike adult blood ves sels, prostacyclin (PGI(2)) 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. Huma n umbilical. veins and arteries were excised; cut into rings and place d in organ chambers filled with 25 mt Krebs-Ringer solution(37 degrees C). 5-hydroxytryptamine (5-HT, 0.01-10 mu M) increased the tension of human umbilical arteries (HUA, from 0.4 +/- 0.2 g to 2.6 +/- 0.4 g) a nd veins (HUV, from 0.8 +/- 0.4 g to 2.5 +/- 0.4 g) in a dose-dependen t manner. DCLHb (0.01-10 mu M) did not have a significant effect on HU A and HUV. Substance P (1 mu M, via prostanoid synthesis) and nitrogly cerin (NG, 1 mu M) but not acetylcholine (ACh, 1 mu M) caused relaxati on of both HUA and HUV. The NO synthase inhibitor L-NA did not have si gnificant effects on HUA and HUV. DCLHb did not alter 5-HT preconstric ted tension of HUA and HUV. The basal cGMP contents of HUA and HUV wer e low. These results support our previous finding that DCLHb-induced v asoconstriction in isolated vessels is dependent primarily on the bind ing of NO by hemoglobin.