This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lauth, M. Articles by Hecker, M. Search for Related Content PubMed PubMed Citation Articles by Lauth, M. Articles by Hecker, M. Related Collections ACE/Angiotension receptors Gene expression Endothelium/vascular type/nitric oxide

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:61.)
© 2001 American Heart Association, Inc.

Vascular Biology

ACE Inhibitor and AT₁ Antagonist Blockade of Deformation-Induced Gene Expression in the Rabbit Jugular Vein Through B₂ Receptor Activation

Manfred Lauth; Marco Cattaruzza; Markus Hecker

From the Department of Cardiovascular Physiology, University of Göttingen, Göttingen, Germany.

Correspondence to Dr Markus Hecker, Department of Cardiovascular Physiology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany. E-mail hecker{at}veg-physiol.med.uni-goettingen.de

Abstract—Deformation-induced endothelin-1 synthesis in endothelial cells may contribute to the intimal hyperplasia of venous bypass grafts. ACE inhibitors and angiotensin II type 1 (AT₁) receptor antagonists are capable of reducing vein graft disease. Therefore, the effects of these drugs on endothelial preproendothelin-1 (ppET-1) and smooth muscle endothelin B receptor (ET_B-R) expression were investigated in isolated perfused segments of the rabbit jugular vein. Pretreatment with ramiprilat (0.3 µmol/L) or irbesartan (0.01 to 1 µmol/L) had no effect on basal ppET-1 or ET_B-R expression but markedly attenuated the deformation-induced expression of these gene products, and these effects were reversed by the B₂ receptor antagonist icatibant (Hoe 140) and by the NO synthase inhibitor N^G-nitro-L-arginine. Candesartan (1 µmol/L) mimicked the inhibitory effect of irbesartan. Moreover, reporter gene analysis with a rat ppET-1 promoter-luciferase construct transiently transfected into porcine aortic cultured endothelial cells revealed that the inhibitory effect of both ramiprilat and irbesartan on deformation-induced ppET-1 expression is species independent and mediated at the level of transcription. In addition, RT-PCR analysis detected only AT₁ receptor expression in the endothelium-intact rabbit jugular vein, and neither irbesartan nor ramiprilat affected endothelial NO synthase expression. Thus, ACE inhibitors and AT₁ receptor antagonists are capable of suppressing deformation-induced gene expression in the vessel wall in both an autocrine (ppET-1) and a paracrine (ET_B-R) manner via a common mechanism of action that constitutes a B₂ receptor–mediated increase in endothelial NO release.

Key Words: blood pressure • endothelin-1 • gene expression • graft failure • nitric oxide

This article has been cited by other articles:

				N. M.S. van den Akker, V. Caolo, L. J. Wisse, P. P.W.M. Peters, R. E. Poelmann, P. Carmeliet, D. G.M. Molin, and A. C. Gittenberger-de Groot Developmental coronary maturation is disturbed by aberrant cardiac vascular endothelial growth factor expression and Notch signalling Cardiovasc Res, May 1, 2008; 78(2): 366 - 375. [Abstract] [Full Text] [PDF]

				B. Rondelet, F. Kerbaul, R. Van Beneden, I. Hubloue, S. Huez, P. Fesler, M. Remmelink, S. Brimioulle, I. Salmon, and R. Naeije Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2319 - H2324. [Abstract] [Full Text] [PDF]