Endothelial Injury from a Circulating Mediator Following Rat Liver Ischemia

Tan, Sidhartha; McAdams, Michelle; Royall, James A.; Freeman, Bruce Α.; Parks, Dale A.

doi:10.1016/s0891-5849(97)00274-8

Cited by 12 publications

(4 citation statements)

References 28 publications

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“…Circulating XO binds to glycosaminoglycan residues on the surface of endothelium in a partially heparin-reversible manner and subsequently translocates to intracellular compartments (Radi et al 1997 ; Houston et al 1999 ). Although mechanisms whereby plasma XO activity is elevated in SHRs are not yet entirely clarified, it has been reported that XO is released from several organs into systemic circulation in a line of pathophysiology including hepatitis, hemorrhagic shock, sickle cell disease, and ischemia reperfusion (Yokoyama et al 1990 ; Tan et al 1998 ; Aslan et al 2001 ). SHRs represent a variety of organ damages related to severe hypertension (Liu et al 2011 ; Boon et al 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats

Saito

Nomura

Matsui

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial. To explore the possible involvement of XO-derived oxidative stress in the pathophysiology of vascular dysfunction, by use of a selective XO inhibitor, febuxostat, we investigated the impact of pharmacological inhibition of XO on hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats (SHRs). Sixteen-week-old SHR and normotensive Wistar-Kyoto (WKY) rats were treated with tap water (control) or water containing febuxostat (3 mg/kg/day) for 6 weeks. Systolic blood pressure (SBP) in febuxostat-treated SHR (220 ± 3 mmHg) was significantly (P < 0.05) decreased compared with the control SHR (236 ± 4 mmHg) while SBP in febuxostat-treated WKY was constant. Acetylcholine-induced endothelium-dependent relaxation in aortas from febuxostat-treated SHR was significantly (P < 0.05) improved compared with the control SHR, whereas relaxation in response to sodium nitroprusside was not changed. Vascular XO activity and tissue nitrotyrosine level, a representative indicator of local oxidative stress, were considerably elevated in the control SHR compared with the control WKY, and this increment was abolished by febuxostat. Our results suggest that exaggerated XO activity and resultant increase in oxidative stress in this experimental model contribute to the hypertension and endothelial dysfunction, thereby supporting a notion that pharmacological inhibition of XO is valuable not only for hyperuricemia but also for treating hypertension and related endothelial dysfunction in human clinics.

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Section: Discussionmentioning

confidence: 99%

Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats

Saito

Nomura

Matsui

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Initially, it was considered that circulating XO could be used as a sensitive marker to quantitate liver injury. Subsequent work by Freeman and colleagues demonstrated that circulating XO is not only a marker of hepatic and intestinal damage, but it can also act as a circulating mediator that is responsible for remote organ injury in a variety of pathophysiological conditions including hepatic ischemia and reperfusion, hemorrhagic shock, atherosclerosis, and sickle cell disease (Yokoyama et al, 1990;Tan et al, 1993bTan et al, , 1995Tan et al, , 1998White et al, 1996; Radi et al, FIG. 2.…”

Section: Introduction Historical Backgroundmentioning

confidence: 99%

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

2006

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“…For example, pulmonary microvascular permeability is increased in nonischemic lungs after perfusion with effluent from reperfused ischemic liver, compared to those lungs perfused with effluent from nonischemic livers, in a double-isolated perfused rat organ model. 3 Severe hepatic ischemia results in heart injury involving systemic inflammatory responses. 4 Interestingly, ischemia and reperfusion injury impair aortic tone, and despite its vasoconstrictor capability, methylene blue provides the aorta with dosedependent protection.…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Synthase in Heart and Thoracic Aorta After Liver Ischemia and Reperfusion Injury: An Experimental Study in Rats

Miranda

Tirapelli²,

Ramos³

et al. 2012

Exp Clin Transplant

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Objectives: We tested the effects of liver reperfusion in the immunohistochemical expression of nitric oxide synthase on the thoracic aorta and the heart. Materials and Methods: We randomized 24 male Wistar rats into 3 groups: (1) control; (2) R2 group, with 60 minutes of partial (70%) liver ischemia and 2 hours of global liver reperfusion; (3) and R6 group, with 60 minutes of partial liver ischemia and 6 hours of global liver reperfusion. Results: In the heart, there was little, diffuse immunohistochemical endothelial staining; immunohistochemical inducible nitric oxide synthase staining was expressed in the adventitia layer of intramyocardial vessels in both cases, with a time-dependent but not statistically significant increase. In the thoracic aorta, a time-dependent decrease in endothelial nitric oxide synthase expression in the muscular layer after reperfusion, which was statistically significant in R6 versus the control. Positive immunostaining for inducible nitric oxide synthase was seen in the muscular and endothelial layers, and this varied from moderate in the control group, to light in the endothelium in groups R2 and R6. Conclusions:We observed changes that may be implicated in heart injury and impairment of aortal tone after liver ischemia and reperfusion injury.

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Endothelial Injury from a Circulating Mediator Following Rat Liver Ischemia

Cited by 12 publications

References 28 publications

Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats

Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats

Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol

Nitric Oxide Synthase in Heart and Thoracic Aorta After Liver Ischemia and Reperfusion Injury: An Experimental Study in Rats

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