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Altered reactivity of tertiary mesenteric arteries following acute myocardial ischemia.

ABSTRACT: It is unknown if cardiac ischemia has any deleterious effect on the contractile properties of nonischemic, peripheral vascular beds. Thus, the objective of the present study was to determine whether acute myocardial ischemia results in peripheral vascular dysfunction.This study characterized force maintenance and the sensitivity to acetylcholine (ACh)-mediated smooth muscle (SM) relaxation of tertiary (3rd) mesenteric arteries from Sprague-Dawley rats following 30 min of myocardial ischemia. Both the phosphorylation of nonmuscle (NM) light chain (LC) and SM-LCs as well as the expression of myosin phosphatase targeting subunit 1 (MYPT1) were also determined. Our data demonstrate that acute myocardial ischemia resulted in vascular dysfunction of 3rd mesenteric vessels, characterized by decreases in force maintenance, ACh- and cGMP-mediated SM relaxation, the phosphorylation of NM-LCs and SM-LCs, and MYPT1 expression. Ischemia was also associated with an increase in protein polyubiquitination, suggesting that during ischemia MYPT1 is targeted for degradation or proteolysis.Acute myocardial ischemia produces peripheral vascular dysfunction; the changes in LC phosphorylation and MYPT1 expression result in a decrease in both tone and the sensitivity to NO-mediated SM relaxation of the peripheral vasculature.

SUBMITTER: Han YS

PROVIDER: S-EPMC3641690 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Altered reactivity of tertiary mesenteric arteries following acute myocardial ischemia.

Han Young Soo YS Brozovich Frank V FV

Journal of vascular research 20121121 2

<h4>Background</h4>It is unknown if cardiac ischemia has any deleterious effect on the contractile properties of nonischemic, peripheral vascular beds. Thus, the objective of the present study was to determine whether acute myocardial ischemia results in peripheral vascular dysfunction.<h4>Methods and results</h4>This study characterized force maintenance and the sensitivity to acetylcholine (ACh)-mediated smooth muscle (SM) relaxation of tertiary (3rd) mesenteric arteries from Sprague-Dawley ra ...[more]

PMID: 23172397

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Project description:BackgroundLittle is known about the microcirculatory alterations in patients with chronic mesenteric ischemia (CMI). We hypothesized that patients with CMI have an impaired microcirculatory function and show an oral microcirculatory response after caloric challenge compared to healthy controls.MethodsAll patients and controls received the standard workup for CMI. Sublingual micro-circulation was evaluated before (T0) and 20 minutes after (T1) feeding. The total vessel density (TVD; mm/mm2), perfused vessel density (PVD; mm/mm2), proportion of perfused vessels (PPV; %) and microvascular flow index (MFI; AU) were assessed.ResultsWe included 12 patients (63.2 years [IQR 48.8-70.4 years], 67% males) and 12 controls (32.7 years [IQR 27.7-38.1 years], 42% males). At baseline, patients with CMI had a decreased PPV of the sublingual small vessels (median 84.8% vs 95.7%, P=0.006), PPV of all vessels (PPV median 85.4% vs 95.3%, P=0.007) and microvascular flow index of all vessels (MFIa; median 3.00 vs 2.80, P=0.039) compared to healthy controls. After caloric challenge, PVD increased significantly in both small vessels (perfused vessel density of the small vessels [PVDs]) and all vessels (perfused vessel density of all vessels [PVDa]; PVDs [T0]) median 16.3 [IQR 13.3-22.1] vs [T1] median 19.9 [IQR 14.2-26.2], P=0.008; PVDa [T0] median 19.1 [IQR 16.2-23.6] vs [T1] median 22.2 [IQR 16.5-28.9], P=0.02; proportion of perfused vessels of the small vessels (PPVs; [T0] median 84.8% [IQR 75.3-90.4] vs [T1] median 91.0% [IQR 80.1-93.8], P=0.010). In contrast, no significant changes in microcirculatory parameters were observed after caloric challenge in healthy controls.ConclusionPatients with CMI have an impaired sublingual microcirculation at baseline and show a significant response in the sublingual microcirculation after caloric challenge, whereas healthy controls have a normal microcirculation at baseline and show no reactive response upon a caloric challenge as seen in CMI patients. Sublingual microcirculation visualization may offer a rapid noninvasive method to identify patients at risk for having CMI.

Project description:ObjectiveRecruitment of neutrophils and formation of neutrophil extracellular traps (NETs) contribute to lethality in acute mesenteric infarction. To study the impact of the gut microbiota in acute mesenteric infarction, we used gnotobiotic mouse models to investigate whether gut commensals prime the reactivity of neutrophils towards formation of neutrophil extracellular traps (NETosis). Approach and Results: We applied a mesenteric ischemia-reperfusion (I/R) injury model to germ-free (GF) and colonized C57BL/6J mice. By intravital imaging, we quantified leukocyte adherence and NET formation in I/R-injured mesenteric venules. Colonization with gut microbiota or monocolonization with Escherichia coli augmented the adhesion of leukocytes, which was dependent on the TLR4 (Toll-like receptor-4)/TRIF (TIR-domain-containing adapter-inducing interferon-β) pathway. Although neutrophil accumulation was decreased in I/R-injured venules of GF mice, NETosis following I/R injury was significantly enhanced compared with conventionally raised mice or mice colonized with the minimal microbial consortium altered Schaedler flora. Also ex vivo, neutrophils from GF and antibiotic-treated mice showed increased LPS (lipopolysaccharide)-induced NETosis. Enhanced TLR4 signaling in GF neutrophils was due to elevated TLR4 expression and augmented IRF3 (interferon regulatory factor-3) phosphorylation. Likewise, neutrophils from antibiotic-treated conventionally raised mice had increased NET formation before and after ischemia. Increased NETosis in I/R injury was abolished in conventionally raised mice deficient in the TLR adaptor TRIF. In support of the desensitizing influence of enteric LPS, treatment of GF mice with LPS via drinking water diminished LPS-induced NETosis in vitro and in the mesenteric I/R injury model.ConclusionsCollectively, our results identified that the gut microbiota suppresses NETing neutrophil hyperreactivity in mesenteric I/R injury, while ensuring immunovigilance by enhancing neutrophil recruitment.

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Altered reactivity of tertiary mesenteric arteries following acute myocardial ischemia.

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Altered reactivity of tertiary mesenteric arteries following acute myocardial ischemia.

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