Effects of hemoglobin-based blood substitutes on vasoactivity of rat aortic rings

Our objective is to characterize the vasoactive properties of a 10% alpha alpha diaspirin cross-linked human hemoglobin (alpha alpha Hb) and to test the hypothesis that sodium nitroprusside (SNP)-induced relaxation is inhibited in the presence of alpha alpha Hb. Experiments were performed on aortic rings from 18 Wistar rats; the rings were suspended in aerated Krebs solution. Changes in isometric tension were measured to increasing concentrations of alpha alpha Hb (1.8 x 10(-9) to 10(-4) M) on phenylephrine (PE)-induced contraction (3 x 10(-7) M), on acetylcholine (ACh)-induced relaxation (10(-8) to 10(-6) M), on SNP-induced relaxation (10(-9) and 10(-8) M), and on PE-induced contraction with an endothelin-1 (ET1) receptor antagonist, BQ123 (10(-5) M). Control rings received no alpha alpha Hb. A concentration-dependent increase of the PE-precontraction (1.3%, 6.8%, 17.4%, and 34%, respectively) as well as the inhibition and reversal of ACh-induced relaxation was observed after alpha alpha Hb. The presence of alpha alpha Hb decreased the SNP-induced relaxation in the presence or absence of endothelium. The relaxation induced by SNP was reduced with time in the presence, but not in the absence, of alpha alpha Hb. In conclusion, although pharmacological modulation of the vasoconstriction is possible with nitric oxide donors, our findings suggest that in the clinical setting, large sustained donor doses may be required.