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 (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.
Highlights
Interruption of blood flow to intestinal tissue caused by thrombi, embolisms, or secondary to other non-occlusive processes (Massberg and Messmer, 1998; Stefanutti et al, 2004) results in ischemic injury to the small intestine
The ability of altered structural and mechanical properties of resistance arteries to contribute to cardiovascular disease (Intengan and Schiffrin, 2001; Martinez-Lemus et al, 2009) raises the theory that the integrity of mesenteric resistance artery (MRA) properties is disrupted after mesenteric I/R
We demonstrated that after 90 min superior mesenteric occlusion followed by 24 h reperfusion, MRA structural and mechanical properties are modified, and we studied the mechanisms underlying those changes
Summary
Interruption of blood flow to intestinal tissue caused by thrombi, embolisms, or secondary to other non-occlusive processes (Massberg and Messmer, 1998; Stefanutti et al, 2004) results in ischemic injury to the small intestine. While reperfusion of ischemic intestine is essential, it leads to a sequence of events known as mesenteric ischemia/reperfusion (I/R) injury, which is a life-threatening clinical complication. Mean arterial pressure returns to control values toward the end of ischemia and decreases during reperfusion (Hayward and Lefer, 1998; Khanna et al, 2001). These results illustrate the complexity of the cardiovascular response during mesenteric I/R and highlights the need for further studies
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