Published online before print May 27, 2004, doi: 10.1161/01.RES.0000133677.77465.38
© 2004 American Heart Association, Inc.
Integrative Physiology |
Contribution of Fluid Shear Response in Leukocytes to Hemodynamic Resistance in the Spontaneously Hypertensive Rat
From the Department of Bioengineering (S.F., N.K., G.W.S.-S.), The Whitaker Institute of Biomedical Engineering University of California San Diego, La Jolla, Calif; and the Department of Integrated Medicine (T.Y., N.I.), Omiya Medical Center, Jichi Medical School, Saitama, Japan.
Correspondence to Dr Geert W. Schmid-Schönbein, Department of Bioengineering, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0412. E-mail gwss{at}bioeng.ucsd.edu
The mechanisms for elevation of peripheral vascular resistance in spontaneously hypertensive rats (SHR), a glucocorticoid-dependent form of hypertension, are unresolved. An increase in hemodynamic resistance caused by circulating blood may be a factor. Physiological fluid shear stress induces a variety of responses in circulating leukocytes, including pseudopod retraction. Due to high rigidity, leukocytes with pseudopods have greater difficulty to pass through capillaries. Because SHR have more circulating leukocytes with pseudopods, we hypothesize that inhibition of the leukocyte shear response by glucocorticoids in SHR impairs normal leukocyte passage through capillaries and causes enhanced resistance in capillary channels. Fluid shear leads to retraction of pseudopods in normal leukocytes, whereas shear induces pseudopod projection in SHR and dexamethasone-treated Wistar rats. The high incidence of circulating leukocytes with pseudopods results in slower cell passage through capillaries under normal blood flow and during reduced flow enhanced capillary plugging both in vivo and in vitro. SHR blood requires higher pressure (90.0±8.2 mm Hg) than Wistar Kyoto rat (WKY, 69.6±6.5 mm Hg; P<0.0001) or adrenalectomized SHR (73.5±2.1 mm Hg; P=0.0009) at the same flow rate in the resting hemodynamically isolated skeletal muscle microcirculation. Intravenous injection of blood from SHR, but not WKY, causes blood pressure increase in normal rats, which depends on pseudopod formation. We conclude that in addition to enhanced vascular tone, pseudopod formation with lack of normal fluid shear response may serve as mechanisms for an elevated hemodynamic resistance in SHR.
Key Words: capillaries • glucocorticoids • pseudopod formation • mechanotransduction
This article has been cited by other articles:
 |
|
 |
|
  B. I. Levy, E. L. Schiffrin, J.-J. Mourad, D. Agostini, E. Vicaut, M. E. Safar, and H. A.J. Struijker-Boudier Impaired Tissue Perfusion: A Pathology Common to Hypertension, Obesity, and Diabetes Mellitus Circulation, August 26, 2008; 118(9): 968 - 976. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Waki, B. Liu, M. Miyake, K. Katahira, D. Murphy, S. Kasparov, and J. F.R. Paton Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats: Evidence for a Prohypertensive Role Within the Brain Stem Hypertension, June 1, 2007; 49(6): 1321 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Makino, M. Glogauer, G. M. Bokoch, S. Chien, and G. W. Schmid-Schonbein Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases Am J Physiol Cell Physiol, April 1, 2005; 288(4): C863 - C871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. DeLano, R. Balete, and G. W. Schmid-Schonbein Control of oxidative stress in microcirculation of spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H805 - H812. [Abstract] [Full Text] [PDF]
|
|