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 (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 (O2⋅−) production, and mRNA levels of NAD(P)H-oxidase subunits were measured. To assess ET-1 effects on O2⋅− 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 O2⋅− 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 O2⋅− (P < 0.05) production in cultured MRA. Tezosentan prevented hypertrophic remodeling and collagen I/III deposition, and enhanced O2⋅− 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 O2⋅−. 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.

The intestinal injury caused by ischemia‐reperfusion is attenuated by amniotic fluid stem cells via the release of tumor necrosis factor‐stimulated gene 6 protein

“…The origin of the SMA was identified, dissected, and occluded for 90 minutes using a silicone loop (Surg‐I‐Loop; Scanlan, Saint Paul, MN) slung around the SMA origin from the aorta. The duration of SMA occlusion is similar to other studies 23‐25 . Occlusion of the SMA, which resulted in intestinal color change, was confirmed by the absence of pulsation in the mesentery at visual inspection and using a dissecting microscope.…”

Sex Differences in the Vasodilation Mediated by G Protein-Coupled Estrogen Receptor (GPER) in Hypertensive Rats

“…The intensity of total vascular fluorescence of anti-GPER and its colocalization with anti-VWF (merge between 488 and 555 filters) was measured in two rings of each animal, normalized by the analyzed area. Results were expressed as arbitrary units ( Caracuel et al, 2012 ).…”

Western-style diet modulates contractile responses to phenylephrine differently in mesenteric arteries from senescence-accelerated prone (SAMP8) and resistant (SAMR1) mice

“…Messenger RNA (mRNA) expression of 1) the nitric oxide synthase isoforms (eNOS, iNOS and nNOS), 2) the subunits of NAD(P)H-oxidase (Nox-1, p22 phox and p47 phox ) and 3) the superoxide dismutase (SOD) isoforms [cytoplasmic Cu, Zn (SOD1), mitochondrial Mn (SOD2) and extracellular Cu, Zn (SOD3)] were quantified by Syber green-based quantitative real-time PCR as previously described (Caracuel et al 2011;Márquez-Martín et al 2012). Primer sequences for rodent genes used in this study are shown in Table 2.…”

“…Frozen sections (14 μm) were incubated with primary antibodies as follows: mouse monoclonal anti-eNOS (1:100; BD Biosciences, Franklin Lakes, NJ, USA) or a rabbit polyclonal anti-iNOS (1:50; Thermo Scientific, Rockford, IL, USA), anti-nNOS (1:100; Life Technologies Ltd, Paisley, UK) and anti-nitrotyrosine (1:100; Merck Millipore, Billerica, MA, USA). Sections were processed for immunofluorescence staining essentially as previously described (Caracuel et al 2011;Jiménez-Altayó et al 2009;Martínez-Revelles et al 2012). Quantitative analysis of fluorescence was performed with MetaMorph Image Analysis software (Molecular Devices, Sunnyvale, CA, USA).…”