Molecular dimensions of Hb-based O₂ carriers determine constriction of resistance arteries and hypertension

The effect of molecular dimension of hemoglobin (Hb)-based O₂ carriers on the diameter of resistance arteries (A₀, 158 ± 21 μm) and arterial blood pressure were studied in the conscious hamster dorsal skinfold model. Cross-linked Hb (XLHb), polyethylene glycol (PEG)-conjugated Hb, hydroxyethylstarch-conjugated XLHb, polymerized XLHb, and PEG-modified Hb vesicles (PEG-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 decrease in A₀ diameter (79 ± 8% of basal value) and a blood flow decrease throughout the microvascular network. The diameter of smaller arterioles did not change significantly. Infusion of larger O₂ carriers resulted in lesser vasoconstriction and hypertension, with PEG-HbV showing the smallest changes. Constriction of resistance arteries was found to be correlated with the level of hypertension, and the responses were proportional to the molecular dimensions of the O₂ carriers. The underlying mechanism is not evident from these experiments; however, it is likely that the effects are related to the diffusion properties of the different Hb molecules.