title: Molecular dimensions of Hb-based O(2) carriers determine constriction of resistance arteries and hypertension.
abstract: The effect of molecular dimension of hemoglobin (Hb)-based O(2) carriers on the diameter of resistance arteries (A(0), 158 +/- 21 microm) 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 A(0) 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 O(2) 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 O(2) 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.
authors.affiliation: Department of Polymer Chemistry, Advanced Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Yuasa
authors.forename: A G
authors.initials: AG
authors.lastname: Tsai
authors.forename: S
authors.initials: S
authors.lastname: Takeoka
authors.forename: E
authors.initials: E
authors.lastname: Tsuchida
authors.forename: M
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects*; D001802:Blood Substitutes / Q000008:administration & dosage / Q000737:chemistry; D006224:Cricetinae; D004337:Drug Carriers; D006454:Hemoglobins / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D008081:Liposomes; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001802:Blood Substitutes; D004337:Drug Carriers; D006454:Hemoglobins; D008081:Liposomes; D011108:Polymers; D011092:Polyethylene Glycols; D010100:Oxygen