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Transient mesenteric ischemia leads to remodeling of rat mesenteric resistance arteries

Abstract:

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 (90min) and reperfused (24h). 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 (O 2.-) production, and mRNA levels of NAD(P)H-oxidase subunits were measured. To assess ET-1 effects on 02~ 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 O 2.- 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 O 2.- (P<0.05) production in cultured MRA. Tezosentan prevented hyper-trophic remodeling and collagen I/III deposition, and enhanced O 2.- production, but it did not affect the decreased wall stiffness after mesenteric I/R. These results indicate that 90min occlusion/24h reperfusion induces hypertrophic remodeling of MRA linked to ET-1-mediated increase of collagen and O 2.-. 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. © 2012 Caracuel, Jiménez- Altayó, Romo, Márquez-Martín, Dantas and Vila.