title: Wall shear stress differentially affects NO level in arterioles for volume expanders and Hb-based O2 carriers.
abstract: The endothelium-derived nitric oxide (NO) is one of the mediators of smooth muscle (SM) relaxation. The release of NO by endothelium depends on the wall shear stress (WSS) to which endothelium is exposed. During hemodilution or isovolemic exchange transfusion with hemoglobin-based oxygen carriers (HBOCs) or volume expanders, the systemic hematocrit, blood viscosity, and blood flow rate are affected that would change WSS at endothelium. The effect of WSS-dependent NO release on SM NO availability has not been determined by direct measurements. We have formulated a mathematical model that is capable of predicting NO concentration in and around arteriolar vessels. The model predicts that the normal physiological SM NO concentration is approximately 100 nM at a physiological WSS of 24 dyn/cm(2) and the NO concentration is linearly dependent on WSS. With volume expanders, the SM NO concentration increases significantly and the levels of SM NO are significantly higher with increase in WSS. The SM NO decreases several-fold even for 5 microM luminal HBOC. For HBOCs, the NO levels are not restored to normal physiological level even with a significant increase in WSS (>48 dyn/cm(2)). These predictions are consistent with the results of animal studies of vascular tone following administration of HBOCs and volume expanders.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. kavdia@bme.jhu.edu
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kavdia
authors.forename: Aleksander S
authors.initials: AS
authors.lastname: Popel
mesh_terms: D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology* / Q000502:physiology; D001808:Blood Vessels / Q000033:anatomy & histology*; D004730:Endothelium, Vascular / Q000033:anatomy & histology* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008833:Microcirculation; D008953:Models, Anatomic; D008962:Models, Theoretical; D009569:Nitric Oxide; D010100:Oxygen / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013314:Stress, Mechanical; D013997:Time Factors; D014664:Vasodilation
chemical_list: D006454:Hemoglobins; D009569:Nitric Oxide; D010100:Oxygen