title: Small artery remodeling and erythrocyte deformability in L-NAME-induced hypertension: role of transglutaminases.
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.
  
  
  RESULTS
  Wild-type (WT) mice and tissue-type transglutaminase (tTG) knockout (KO) mice received the nitric oxide inhibitor Nomega-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/cm(2), p = 0.014) but not in the tTG KO mice.
  
  
  CONCLUSIONS
  Transglutaminases are involved in small artery inward remodeling and erythrocyte stiffening associated with nitric oxide inhibition-related hypertension.
authors: Department of Medical Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Adrian
authors: A
authors: Pistea
authors: Erik N T P
authors: EN
authors: Bakker
authors: Jos A E
authors: JA
authors: Spaan
authors: Max R
authors: MR
authors: Hardeman
authors: Nico
authors: N
authors: van Rooijen
authors: Ed
authors: E
authors: VanBavel
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004002:Clodronic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D004907:Erythrocyte Deformability; D005176:Factor XIII / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006400:Hematocrit; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008638:Mesenteric Arteries / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012107:Research Design; D013314:Stress, Mechanical; D013997:Time Factors; D011503:Transglutaminases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D004002:Clodronic Acid; D009569:Nitric Oxide; D005176:Factor XIII; D019001:Nitric Oxide Synthase; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D019331:NG-Nitroarginine Methyl Ester