Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion

• Published in: American journal of physiology. Heart and circulatory physiology 2005-04, Vol.288 (4), p.H1730-H1739
• Main Authors: Tsai, Amy G, Acero, Cesar, Nance, Patricia R, Cabrales, Pedro, Frangos, John A, Buerk, Donald G, Intaglietta, Marcos
• Format: Article
• Language: English
• Subjects: Animals; Arterioles - physiology; Blood Pressure - physiology; Blood Viscosity - drug effects; Blood Viscosity - physiology; Capillaries - physiology; Cricetinae; Dextrans - pharmacology; Hemodilution; Mesocricetus; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III; Osmotic Pressure; Oxygen - blood; Plasma Substitutes - pharmacology; Skin - blood supply; Stress, Mechanical; Venules - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00998.2004

1 Department of Bioengineering, University of California, San Diego, La Jolla; 2 La Jolla Bioengineering Institute, La Jolla, California; and 3 Departments of Physiology and Bioengineering and the Institute of Environmental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania Submitted 29 September 2004 ; accepted in final form 29 November 2004 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. functional capillary density; microvascular flow; shear stress; plasma expanders; mechanotransduction Address for reprint requests and other correspondence: A. G. Tsai, Dept. of Bioengineering, 9500 Gilman Dr., Univ. of California-San Diego, La Jolla, CA 92093-0412 (E-mail: agtsai{at}ucsd.edu )