Research Paper

Small Artery Remodeling and Erythrocyte Deformability in L-NAME-Induced Hypertension: Role of Transglutaminases
Adrian Pistea^a, Erik N.T.P. Bakker^a, Jos A.E. Spaan^a, Max R. Hardeman^b, Nico van Rooijen^c, Ed VanBavel^a

Departments of
^aMedical Physics and
^bPhysiology, Academic Medical Center, University of Amsterdam, and
^cDepartment of Molecular Cell Biology, Faculty of Medicine, Free University of Amsterdam, Amsterdam, The Netherlands

Address of Corresponding Author

J Vasc Res 2008;45:10-18 (DOI: 10.1159/000109073)

  Key Words

• Vascular remodeling
• Transglutaminase
• Coagulation factor XIII
• Resistance arteries
• Hypertension
• Nitric oxide
• Knockout mice
• Erythrocyte deformability

  Abstract

Background: Hypertension is associated with inward remodeling of small arteries and decreased erythrocyte deformability, both impairing proper tissue perfusion. We hypothesized that these alterations depend on transglutaminases, cross-linking enzymes present in the vascular wall, monocytes/macrophages and erythrocytes. Methods and Results: Wild-type (WT) mice and tissue-type transglutaminase (tTG) knockout (KO) mice received the nitric oxide inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) to induce hypertension. After 1 week, mesenteric arteries from hypertensive WT mice showed a smaller lumen diameter (-6.9 ± 2.0%, p = 0.024) and a larger wall-to-lumen ratio (11.8 ± 3.5%, p = 0.012) than controls, whereas inward remodeling was absent in hypertensive tTG KO mice. After 3 weeks, the wall-to-lumen ratio was increased in WT (20.8 ± 4.8%, p = 0.005) but less so in tTG KO mice (11.7 ± 4.6%, p = 0.026), and wall stress was normalized in WT but not in tTG KO mice. L-NAME did not influence expression of tTG or an alternative transglutaminase, coagulation factor XIII (FXIII). Suppression of FXIII by macrophage depletion was associated with increased tTG in the presence of L-NAME. L-NAME treatment decreased erythrocyte deformability in the WT mice (-15.3% at 30 dynes/cm², p = 0.014) but not in the tTG KO mice. Conclusion: Transglutaminases are involved in small artery inward remodeling and erythrocyte stiffening associated with nitric oxide inhibition-related hypertension.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Dr. Ed VanBavel
Department of Medical Physics, Academic Medical Center
University of Amsterdam, PO Box 22700
NL-1100 DE Amsterdam (The Netherlands)
Tel. +31 20 566 5203, Fax +31 20 691 7233, E-Mail e.vanbavel@amc.uva.nl

  Article Information

Received: January 23, 2007
Accepted after revision: June 1, 2007
Published online: September 26, 2007
Number of Print Pages : 9
Number of Figures : 5, Number of Tables : 1, Number of References : 45