TY - JOUR
T1 - Molecular dimensions of Hb-based O2 carriers determine constriction of resistance arteries and hypertension
AU - Sakai, Hiromi
AU - Hara, Hiroyuki
AU - Yuasa, Minako
AU - Tsai, Amy G.
AU - Takeoka, Shinji
AU - Tsuchida, Eishun
AU - Intaglietta, Marcos
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Auto-regulation
KW - Blood substitutes
KW - Hemoglobin
KW - Microcirculation
KW - Nitric oxide
KW - Resistance vessels
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U2 - 10.1152/ajpheart.2000.279.3.h908
DO - 10.1152/ajpheart.2000.279.3.h908
M3 - Article
C2 - 10993749
AN - SCOPUS:0033830643
VL - 279
SP - H908-H915
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 3 48-3
ER -