Hypertension Research Today is a free monthly online journal that collates and summarizes the latest research about Hypertension, including details on symptoms, diagnosis, diet, treatment, causes. | ||||||||
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Small artery remodeling and erythrocyte deformability in L-NAME-induced hypertension: role of transglutaminases.Pistea A, Bakker EN, Spaan JA, Hardeman MR, van Rooijen N, VanBavel E Department of Medical Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 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 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. CONCLUSION: Transglutaminases are involved in small artery inward remodeling and erythrocyte stiffening associated with nitric oxide inhibition-related hypertension. Published 18 December 2007 in J Vasc Res, 45(1): 10-8.
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