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Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm

  • Author(s): Waeckel, L
  • Badier-Commander, C
  • Damery, T
  • Köhler, R
  • Sansilvestri-Morel, P
  • Simonet, S
  • Vayssettes-Courchay, C
  • Wulff, H
  • Félétou, M
  • et al.

Published Web Location

https://link.springer.com/article/10.1007/s00424-014-1644-6
No data is associated with this publication.
Abstract

© Springer-Verlag Berlin Heidelberg 2014. Angiotensin-II and oxidative stress are involved in the genesis of aortic aneurysms, a phenomenon exacerbated by endothelial nitric oxide synthase (eNOS) deletion or uncoupling. The purpose of this work was to study the endothelial function in wild-type C57BL/6 (BL) and transgenic mice expressing the h-angiotensinogen and h-renin genes (AR) subjected to either a control, or a high-salt diet plus a treatment with a NO-synthase inhibitor, N-ω-nitro-L-argininemethyl- ester (L-NAME; BLSL and ARSL). BLSL showed a moderate increase in blood pressure, while ARSL became severely hypertensive. Seventy-five percent of ARSL developed aortic aneurysms, characterized by major histomorphological changes and associated with an increase in NADP(H) oxidase-2 (NOX2) expression. Contractile responses (KCl, norepinephrine, U-46619) were similar in the four groups of mice, and relaxations were not affected in BLSL and AR. However, in ARSL, endothelium-dependent relaxations (acetylcholine, UK-14304) were significantly reduced, and this dysfunction was similar in aortae without or with aneurysms. The endothelial impairment was unaffected by catalase, superoxide-dismutase mimetic, radical scavengers, cyclooxygenase inhibition, or TP-receptor blockade and could not be attributed to sGC oxidation. Thus, ARSL is a severe hypertension model developing aortic aneurysm. A vascular dysfunction, involving both endothelial (reduced role of NO) and smooth muscle cells, precedes aneurysms formation and, paradoxically, does not appear to involve oxidative stress.

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