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

L. Waeckel, C. Badier-Commander, T. Damery, Ralf Köhler, P. Sansilvestri-Morel, S. Simonet, Christine Vayssettes-Courchay, H. Wulff, M. Feletou

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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-omega-nitro-l-arginine-methyl-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 histo-morphological 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.
OriginalsprogEngelsk
TidsskriftPflügers Archiv - European Journal of Physiology
Vol/bind467
Udgave nummer9
Sider (fra-til)1945-1963
ISSN0031-6768
DOI
StatusUdgivet - 2015

Emneord

  • Hypertension Aneurysms Endothelium-dependent and independent vasodilatation Oxidative stress Guanylyl cyclase SOLUBLE GUANYLYL CYCLASE NITRIC-OXIDE SYNTHASE E-DEFICIENT MICE SYSTEMIC VASODILATOR RESPONSES HUMAN ANGIOTENSINOGEN GENES LOWERS BLOOD-PRESSURE SMOOTH-MUSCLE-CELLS MARFAN-SYNDROME ENDOTHELIAL DYSFUNCTION OXIDATIVE STRESS

Citer dette

Waeckel, L., Badier-Commander, C., Damery, T., Köhler, R., Sansilvestri-Morel, P., Simonet, S., ... Feletou, M. (2015). Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm. Pflügers Archiv - European Journal of Physiology, 467(9), 1945-1963. https://doi.org/10.1007/s00424-014-1644-6
Waeckel, L. ; Badier-Commander, C. ; Damery, T. ; Köhler, Ralf ; Sansilvestri-Morel, P. ; Simonet, S. ; Vayssettes-Courchay, Christine ; Wulff, H. ; Feletou, M. / Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm. I: Pflügers Archiv - European Journal of Physiology. 2015 ; Bind 467, Nr. 9. s. 1945-1963.
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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-omega-nitro-l-arginine-methyl-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 histo-morphological 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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Waeckel, L, Badier-Commander, C, Damery, T, Köhler, R, Sansilvestri-Morel, P, Simonet, S, Vayssettes-Courchay, C, Wulff, H & Feletou, M 2015, 'Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm', Pflügers Archiv - European Journal of Physiology, bind 467, nr. 9, s. 1945-1963. https://doi.org/10.1007/s00424-014-1644-6

Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm. / Waeckel, L.; Badier-Commander, C.; Damery, T.; Köhler, Ralf; Sansilvestri-Morel, P.; Simonet, S.; Vayssettes-Courchay, Christine; Wulff, H.; Feletou, M.

I: Pflügers Archiv - European Journal of Physiology, Bind 467, Nr. 9, 2015, s. 1945-1963.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Vascular dysfunctions in the isolated aorta of double-transgenic hypertensive mice developing aortic aneurysm

AU - Waeckel, L.

AU - Badier-Commander, C.

AU - Damery, T.

AU - Köhler, Ralf

AU - Sansilvestri-Morel, P.

AU - Simonet, S.

AU - Vayssettes-Courchay, Christine

AU - Wulff, H.

AU - Feletou, M.

N1 - 0 25385304

PY - 2015

Y1 - 2015

N2 - 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-omega-nitro-l-arginine-methyl-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 histo-morphological 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.

AB - 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-omega-nitro-l-arginine-methyl-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 histo-morphological 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.

KW - Hypertension Aneurysms Endothelium-dependent and independent vasodilatation Oxidative stress Guanylyl cyclase SOLUBLE GUANYLYL CYCLASE NITRIC-OXIDE SYNTHASE E-DEFICIENT MICE SYSTEMIC VASODILATOR RESPONSES HUMAN ANGIOTENSINOGEN GENES LOWERS BLOOD-PRESSURE

U2 - 10.1007/s00424-014-1644-6

DO - 10.1007/s00424-014-1644-6

M3 - Journal article

VL - 467

SP - 1945

EP - 1963

JO - Pflügers Archiv - European Journal of Physiology

JF - Pflügers Archiv - European Journal of Physiology

SN - 0031-6768

IS - 9

ER -