title: Model of nitric oxide diffusion in an arteriole: impact of hemoglobin-based blood substitutes.
abstract: Administration of hemoglobin-based oxygen carriers (HBOCs) frequently results in vasoconstriction that is primarily attributed to the scavenging of endothelium-derived nitric oxide (NO) by cell-free hemoglobin. The ensuing pressor response could be caused by the high NO reactivity of HBOC in the vascular lumen and/or the extravasation of hemoglobin molecules. There is a need for quantitative understanding of the NO interaction with HBOC in the blood vessels. We developed a detailed mathematical model of NO diffusion and reaction in the presence of an HBOC for an arteriolar-size vessel. The HBOC reactivity with NO and degree of extravasation was studied in the range of 2-58 x 10(6) M(-1) x s(-1) and 0-100%, respectively. The model predictions showed that the addition of HBOC reduced the smooth muscle (SM) NO concentration in the activation range (12-28 nM) for soluble guanylate cyclase, a major determinant of SM contraction. The SM NO concentration was significantly reduced when the extravasation of HBOC molecules was considered. The myoglobin present in the parenchymal cells scavenges NO, which reduces the SM NO concentration.
authors: Department of Biomedical Engineering and Center for Computational Medicine and Biology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA. kavdia@bme.jhu.edu
authors: Mahendra
authors: M
authors: Kavdia
authors: Nikolaos M
authors: NM
authors: Tsoukias
authors: Aleksander S
authors: AS
authors: Popel
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D001802:Blood Substitutes; D006224:Cricetinae; D004058:Diffusion; D004730:Endothelium, Vascular / Q000378:metabolism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D006454:Hemoglobins; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D009211:Myoglobin / Q000032:analysis / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D009211:Myoglobin; D009569:Nitric Oxide; D006162:Guanylate Cyclase