Molecular dimensions of Hb-based O-2 carriers determine constriction of resistance arteries and hypertension

The effect of molecular dimension of hemoglobin (Hb)-based O-2 carriers on the diameter of resistance arteries (A(0), 158 +/- 21 mu m) and arterial bl ood pressure were studied in the conscious hamster dorsal skinfold model. C ross-linked Hb (XLHb), polyethylene glycol (PEG)-conjugated Hb, hydroxyethy lstarch-conjugated XLHb, polymerized XLHb, and PEG-modified Hb vesicles (PE G-HbV) were synthesized. Their molecular diameters were 7, 22, 47, 68, and 224 nm, respectively. The bolus infusion of 7 ml/kg of XLHb (5 g/dl) caused an immediate hypertension (+34 +/- 13 mmHg at 3 h) with a simultaneous dec rease in A(0) diameter (79 +/- 8% of basal value) and a blood flow decrease throughout the microvascular network. The diameter of smaller arterioles d id not change significantly. Infusion of larger O-2 carriers resulted in le sser vasoconstriction and hypertension, with PEG-HbV showing the smallest c hanges. Constriction of resistance arteries was found to be correlated with the level of hypertension, and the responses were proportional to the mole cular dimensions of the O-2 carriers. The underlying mechanism is not evide nt from these experiments; however, it is likely that the effects are relat ed to the diffusion properties of the different Hb molecules.