Transient Mesenteric Ischemia Leads to Remodeling of Rat Mesenteric Resistance Arteries
Caracuel Cano, Laura (Universitat Autònoma de Barcelona. Institut de Neurociències)
Jiménez Altayó, Francesc (Universitat Autònoma de Barcelona. Institut de Neurociències)
Romo, Mónica (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Márquez-Martín, Ana (Universitat Autònoma de Barcelona. Institut de Neurociències)
Dantas, A. P. (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Vila Calsina, Elisabet (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2012
Resum:	Mesenteric ischemia/reperfusion (I/R) is associated with high rates of morbidity and mortality. We studied the effect of mesenteric I/R on structural and mechanical properties of rat mesenteric resistance artery (MRA) that, once disrupted, might impact the outcome of this devastating clinical condition. Superior mesenteric artery from Wistar-Kyoto rats was occluded (90 min) and reperfused (24 h). The effect of tezosentan, a dual endothelin (ET)-receptor antagonist, was studied in ischemic (IO) and sham-operated (SO) animals. MRA structure and mechanics were assessed by pressure myography. Nuclei distribution, elastin content and organization, collagen I/III and ET-1 expression, ET-1 plasma levels, superoxide anion () production, and mRNA levels of NAD(P)H-oxidase subunits were measured. To assess ET-1 effects on production, MRA from non-operated rats were incubated in culture medium with ET-1. Mesenteric I/R increased MRA wall thickness (P < 0. 05) and cross-sectional area (P < 0. 05) but decreased wall stiffness (P < 0. 05). Arterial remodeling was paralleled by enhancement of: (i) collagen I/III expression (P < 0. 01), ET-1 expression (P < 0. 05), and formation (P < 0. 01) in the vessel wall; (ii) number of internal elastic lamina (IEL) fenestrae (P < 0. 05); and (iii) plasma levels of ET-1 (P < 0. 05). Moreover, ET-1 increased (P < 0. 05) production in cultured MRA. Tezosentan prevented hypertrophic remodeling and collagen I/III deposition, and enhanced production, but it did not affect the decreased wall stiffness after mesenteric I/R. These results indicate that 90 min occlusion/24 h reperfusion induces hypertrophic remodeling of MRA linked to ET-1-mediated increase of collagen and . Decreased stiffness may be associated with increased number of IEL fenestrae. The resulting MRA remodeling, initially adaptive, might become maladaptive contributing to the pathology and poor outcome of mesenteric I/R, and might be a valuable treatment target for mesenteric I/R.
Ajuts:	Ministerio de Ciencia e Innovación SAF 2007-60406
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Ischemia/reperfusion ; Structural and mechanical properties ; Oxidative stress ; Endothelin
Publicat a:	Frontiers in physiology, Vol. 2 (january 2012) , ISSN 1664-042X

DOI: 10.3389/fphys.2011.00118
PMID: 22291659

11 p, 2.1 MB

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