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• W2020291732 abstract "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 (AT 1 ) 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 B 2 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 AT 1 receptor expression in the endothelium-intact rabbit jugular vein, and neither irbesartan nor ramiprilat affected endothelial NO synthase expression. Thus, ACE inhibitors and AT 1 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 B 2 receptor–mediated increase in endothelial NO release." @default.
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• W2020291732 modified "2023-09-27" @default.
• W2020291732 title "ACE Inhibitor and AT ₁ Antagonist Blockade of Deformation-Induced Gene Expression in the Rabbit Jugular Vein Through B ₂ Receptor Activation" @default.
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• W2020291732 doi "https://doi.org/10.1161/01.atv.21.1.61" @default.
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