title: Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion.
abstract: We tested the hypothesis that high-viscosity (HV) plasma in extreme hemodilution causes wall shear stress to be greater than low-viscosity (LV) plasma, leading to enhanced production of nitric oxide (NO). The perivascular concentration of NO was measured in arterioles and venules and the tissue of the hamster chamber window model, subjected to acute extreme hemodilution, with a hematocrit (Hct) of 11% using Dextran 500 (n = 6) or Dextran 70 (n = 5) with final plasma viscosities of 1.99 +/- 0.11 and 1.33 +/- 0.04 cp, respectively. HV plasma significantly increased the periarteriolar, perivenular, and tissue NO concentration by 2.0, 1.9, and 1.4 times the control (n = 7). The NO concentration with LV plasma was not statistically different from control. Arteriolar shear stress was significantly increased in HV plasma relative to LV plasma in arterioles but not in venules. Aortic endothelial NO synthase (eNOS) protein expression was increased with HV plasma but not with LV plasma. There was a weak correlation between perivascular NO concentration and the locally calculated shear stress induced by the procedures, when blood viscosity was corrected according to Hct values previously determined in studies of microvascular Hct distribution. The finding that the periarteriolar and venular NO concentration in HV plasma was the same although arteriolar shear stress was significantly greater than venular shear stress maybe be due to differences in vessel wall metabolism between arterioles and venules and the presence of NO transport through the blood stream in the microcirculation. Results support the concept that in extreme hemodilution HV plasma maintains functional capillary density through a NO-mediated vasodilatation.
authors.affiliation: Dept. of Bioengineering, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA. agtsai@ucsd.edu
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Cesar
authors.initials: C
authors.lastname: Acero
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Nance
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: John A
authors.initials: JA
authors.lastname: Frangos
authors.forename: Donald G
authors.initials: DG
authors.lastname: Buerk
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001809:Blood Viscosity / Q000187:drug effects / Q000502:physiology*; D002196:Capillaries / Q000502:physiology; D006224:Cricetinae; D003911:Dextrans / Q000494:pharmacology; D006438:Hemodilution; D008647:Mesocricetus; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009997:Osmotic Pressure; D010100:Oxygen / Q000097:blood; D010952:Plasma Substitutes / Q000494:pharmacology; D012867:Skin / Q000098:blood supply*; D013314:Stress, Mechanical; D014699:Venules / Q000502:physiology
chemical_list: D003911:Dextrans; D010952:Plasma Substitutes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen