Endothelin receptor blockers protect against ischemia/reperfusion impairment of gastrointestinal motility in rats

Ługowska-Umer, Hanna; Umer, Artur; Anand, Jacek Sein; Sokołowska‐Wojdyło, Małgorzata; Włodarkiewicz, Adam; Korolkiewicz, Roman

doi:10.1016/j.phrs.2008.04.003

Cited by 17 publications

(22 citation statements)

References 28 publications

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“…Furthermore, treatment with a dual ET receptor antagonist 1 h before vessel occlusion might exert beneficial hemodynamic effects after mesenteric I/R through prevention of hypertrophy and preservation of distensibility in MRA. Our study opens up a potential new avenue for reducing the harmful consequences of I/R, implicates ET-1 and oxidative stress in vascular remodeling observed after mesenteric I/R, and contributes to understanding the mechanism by which ET receptor antagonists exert their beneficial effects on mesenteric I/R (Lugowska-Umer et al, 2008). …”

Section: Discussionmentioning

confidence: 70%

“…injection of tezosentan (TZS, 10 mg/Kg dissolved in saline) on some of the parameters studied was studied in both IO and SO rats. The ET receptor antagonist was administered 1 h before starting the surgical procedure described above, using a dose that has been described as having positive effects on mesenteric I/R (Lugowska-Umer et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

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Transient Mesenteric Ischemia Leads to Remodeling of Rat Mesenteric Resistance Arteries

Caracuel¹,

Jiménez‐Altayó²,

Romo³

et al. 2012

Front. Physio.

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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.

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Section: Discussionmentioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Transient Mesenteric Ischemia Leads to Remodeling of Rat Mesenteric Resistance Arteries

Caracuel¹,

Jiménez‐Altayó²,

Romo³

et al. 2012

Front. Physio.

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“…Restoring blood flow to ischaemic tissue, a major therapeutic goal in the treatment of arterial occlusion, often leads to both local and ischaemic organ damage, called I/R injury (Zimmerman and Granger, 1992). There is evidence that ET‐1 levels increase in the first few hours of reperfusion (Ługowska‐Umer et al ., 2008) and seem to play an important role in the disturbances following I/R (Brunner et al ., 2006). Increased ET‐1 plasma concentration has been reported after I/R in humans (Ziv et al ., 1992; Brondani et al ., 2007) and in rat models of cerebral (Barone et al ., 1993), cardiac (Brunner et al ., 2006) and mesenteric (Büyükgebiz et al ., 1995; Oktar et al ., 2002; Wang et al ., 2006, Guzmán‐de la Garza et al ., 2009) ischaemia.…”

Section: Discussionmentioning

confidence: 99%

“…Contractile responses to ET‐1 have been described as increased in rat heart (García‐Villalón et al ., 2008) and middle cerebral artery (MCA) (Stenman et al ., 2002) after I/R, while a decreased response in mesenteric arteries from deoxycorticosterone acetate salt hypertensive rats (Deng and Schiffrin, 1992) has been shown. Moreover, increased levels of plasma ET‐1 concentration after intestinal I/R have been consistently reported (Kurtel and Ghandhour, 1999; Oktar et al ., 2002; Guzmán‐de la Garza et al ., 2009), although very few studies have analysed the influence of I/R on ET‐1 vasoconstrictor responses (Wood et al ., 1995, 1996; Ługowska‐Umer et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

Increased endothelin‐1 vasoconstriction in mesenteric resistance arteries after superior mesenteric ischaemia‐reperfusion

Martínez-Revelles

Caracuel

Márquez-Martín

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSE Endothelin‐1 (ET‐1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia‐reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET‐1. EXPERIMENTAL APPROACH SMA from male Sprague‐Dawley rats was occluded (90 min) and following reperfusion (24 h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O2•−) production and ET‐1 plasma concentration were evaluated by immunofluorescence, real‐time quantitative PCR, ethidium fluorescence and elisa, respectively. KEY RESULTS I/R increased ET‐1 plasma concentration, ET‐1‐mediated vasoconstriction and ETB mRNA expression, and down‐regulated ETA mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ETB receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ETB receptor agonist sarafotoxin‐6 induced a contraction that was inhibited by the ETB receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET‐1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET‐1 vasoconstriction by BQ788. Endothelium removal, Nω‐nitro‐L‐arginine methyl ester and superoxide dismutase abolished the differences in ET‐1 vasoconstriction between sham and I/R rats. We also found that I/R down‐regulates endothelial NOS mRNA expression and concomitantly enhanced O2•− production by increasing NADPH oxidase 1 (NOX‐1) and p47phox mRNA. CONCLUSIONS AND IMPLICATIONS Mesenteric I/R potentiated the ET‐1‐mediated vasoconstriction by a mechanism that involves up‐regulation of muscular ETB receptors and decrease in NO bioavailability.

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“…Tezosentan, a dual ET receptor antagonist, was proved to be effective in the treatment of IR injury-induced myocardial, pulmonary, renal and intestinal injury (Wilhelm et al 2001;Clozel et al 2002;Kurzelewski et al 2002;Lugowska-Umer et al 2008). Mitsuoka et al (1999) demonstrated that ET receptor antagonism by TAK-044 successfully attenuated the development of pulmonary edema in rats subjected to intestinal IR through to preventive effect on the activation of the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

Endothelin Receptor Blockade with Tezosentan Ameliorates Myocardial Injury Induced by Abdominal Aortic Ischemia-Reperfusion

Narin

Kiriş

Gülmen

et al. 2008

Tohoku J. Exp. Med.

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Endothelin is both a potent vasoconstrictor and an important mediator of ischemia-reperfusion (IR) injury. Therefore, the role of endothelin receptor antagonism in IR-inducedtissue injury carries great interest. Here, we examined the effect of tezosentan, a nonselective antagonist for endothelin receptors, on myocardial injury induced by abdominal aortic IR, which represents a model of the IR injury in distant organs frequently occurred after vascular surgery. Thirty-two Wistar rats were randomized into four groups (n = 8) as follows: control (sham laparotomy), aortic IR (120 min ischemia and 120 min reperfusion), aortic IR + tezosentan (10 mg/kg intravenous injection before ischemia plus continuous intravenous infusion of 1 mg/kg/hr during the IR injury), and control + tezosentan. Biochemical analysis showed that aortic IR significantly increased ( p < 0.05 vs control) the plasma levels of troponin-I, interleukin-6 and tumor necrosis factor-alpha, and the myocardial tissue levels of malondialdehyde, superoxide dismutase and catalase, whereas tezosentan significantly decreased these same factors ( p < 0.05 vs aortic IR). Histological evaluation also showed that aortic IR significantly increased ( p < 0.05 vs control) myocardial disorganization, myofiber swelling and myofiber eosinophilia in myocardial tissue samples, whereas tezosentan significantly decreased these factors ( p < 0.05 vs aortic IR). These results indicate that tezosentan has protective effects against myocardial injury induced by abdominal aortic IR in rats. We propose that the mechanisms underlying this protective effect of tezosentan involves the reduction of oxidative stress and subsequent lipid peroxidation, the inhibition of systemic inflammatory response, and acting cytoprotective on myocytes after aortic IR.Abdominal aortic surgery; reperfusion injury; reactive oxygen species; acute-phase reaction; endothelin-1. Tohoku

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Endothelin receptor blockers protect against ischemia/reperfusion impairment of gastrointestinal motility in rats

Cited by 17 publications

References 28 publications

Transient Mesenteric Ischemia Leads to Remodeling of Rat Mesenteric Resistance Arteries

Transient Mesenteric Ischemia Leads to Remodeling of Rat Mesenteric Resistance Arteries

Increased endothelin‐1 vasoconstriction in mesenteric resistance arteries after superior mesenteric ischaemia‐reperfusion

Endothelin Receptor Blockade with Tezosentan Ameliorates Myocardial Injury Induced by Abdominal Aortic Ischemia-Reperfusion

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