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

Ludovic Waeckel, Cécile Badier-Commander, Thibaut Damery, Ralf Köhler, Patricia Sansilvestri-Morel, Serge Simonet, Christine Vayssettes-Courchay, Heike Wulff, Michel Félétou

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5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberA011
Pages (from-to)1945-1963
Number of pages19
JournalPflugers Archiv European Journal of Physiology
Volume467
Issue number9
DOIs
StatePublished - 2015

Keywords

  • Aneurysms
  • Endothelium-dependent and independent vasodilatation
  • Guanylyl cyclise
  • Hypertension
  • Oxidative stress

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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    Waeckel, L., Badier-Commander, C., Damery, T., Köhler, R., Sansilvestri-Morel, P., Simonet, S., Vayssettes-Courchay, C., Wulff, H., & Félétou, M. (2015). Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm. Pflugers Archiv European Journal of Physiology, 467(9), 1945-1963. [A011]. https://doi.org/10.1007/s00424-014-1644-6