Accumulation of Nitrotyrosine Correlates with Endothelial NO Synthase in Pulmonary Resistance Arteries During Chronic Hypoxia in the Rat

Demiryürek, A. Tuncay; Karamsetty,; McPhaden, AR; Wadsworth, R. M.; Kane, Kathleen A.; MacLean, Margaret R.

doi:10.1006/pupt.2000.0238

Cited by 27 publications

(24 citation statements)

References 27 publications

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“…As in the previous cases, the treatment with the inhibitor L-NIO did not alter bulk-nitrated protein expression, suggesting that eNOS-derived NO may not be involved in the formation of nitrotyrosine in the hypoxic rat heart. Contrary to these results, it has been reported that the up-regulation of eNOS during chronic hypoxia leads to the formation of nitrotyrosine in the endothelium of the pulmonary arteries (Demiryürek et al 2000). In short, the results of this study indicate that treatment with the selective eNOS inhibitor L-NIO does not affect parameters of cell and tissue damage (lipid peroxidation, apoptosis and nitrated protein expression) in the rat heart submitted to H/R.…”

Section: Discussioncontrasting

confidence: 99%

Is endothelial-nitric-oxide-synthase-derived nitric oxide involved in cardiac hypoxia/reoxygenation-related damage?

et al. 2011

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Nitric oxide (NO) has been reported to act both as a destructive and a protective agent in the pathogenesis of the injuries that occur during hypoxia/reoxygenation (H/R). It has been suggested that this dual role of NO depends directly on the isoform of NO synthase (NOS) involved. In this work, we investigate the role that NO derived from endothelial NOS (eNOS) plays in cardiac H/R-induced injury. Wistar rats were submitted to H/R (hypoxia for 30 min; reoxygenation of 0 h, 12 h and 5 days), with or without prior treatment using the selective eNOS inhibitor L-NIO (20 mg/kg). Lipid peroxidation, apoptosis and protein nitration, as well as NO production (NOx), were analysed. The results showed that L-NIO administration lowered NOx levels in all the experimental groups. However, no change was found in the lipid peroxidation level, the percentage of apoptotic cells or nitrated protein expression, implying that eNOS-derived NO may not be involved in the injuries occurring during H/R in the heart. We conclude that LNIO would not be useful in alleviating the adverse effects of cardiac H/R.

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Section: Discussioncontrasting

confidence: 99%

Is endothelial-nitric-oxide-synthase-derived nitric oxide involved in cardiac hypoxia/reoxygenation-related damage?

et al. 2011

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“…Although eNOS expression increases after exposure to hypoxia for 2 days and remained elevated at 7 and 14 days exposure in the conduit artery, the expression progressively increased after 7 and 14 days exposure in resistance arteries [34,35]. These findings suggest that up-regulation of eNOS in resistance arteries may modify the ET and renin-angiotensin system mediated vascular remodelling [35].…”

Section: Discussionmentioning

confidence: 83%

“…Endothelial nitric oxide (NO), another important smooth muscle tone regulator is produced by endothelial NO synthase (eNOS). In normoxic rats, eNOS is expressed in the endothelium of both resistance and conduit pulmonary arteries [34].…”

Section: Discussionmentioning

confidence: 99%

Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery

et al. 2001

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Since pulmonary vasculature is complex in terms of regional difference in structure and function, it is important to understand the site of endothelin (ET) synthesis and the distribution of the ET system along the axial pathways of pulmonary artery.The expression of big ET-1, ET converting enzyme (ECE) and ETA receptors were examined in rat pulmonary arteries under normal and hypoxic conditions using an immunohistochemical method and Northern blot analysis.In normal conditions, big ET-1 was expressed in the intima and media of pulmonary arteries with a predominant distribution in the distal segments and a preferential localization in the media, while ETA receptors were dominantly expressed in the proximal segments. ECE was constitutively expressed in the intima and media. Following exposure to hypoxia, messenger ribonucleic acid (mRNA) expression of ET-1 and ETA receptors were up-regulated by two-fold and immunoreactivities for big ET-1, ECE, and ETA receptors significantly increased by two to five-fold in the distal segments.Smooth muscle cells are an important source of endothelin-1 in the pulmonary artery. The distribution of big endothelin-1 and endothelin A receptors in pulmonary arteries was discrepant in normal conditions while their expression concomitantly increased in the distal segments in hypoxic conditions. This heterogeneity may play an important role in the regulation of pulmonary vascular tone. Endothelins (ETs) and their receptors are abundantly expressed in the lung and postulated to play an important role in the regulation of pulmonary vascular tone. ET-l, a potent vasoconstrictor and smooth muscle mitogen composed of 21 amino acids, is synthesized from big ET-l by a specific cleavage at Trp 21 -Val 22 by ET converting enzyme (ECE) [l, 2]. The actions of ET-l are mediated by two different receptors, ETA and ETB receptors [1,2]. ETA receptors are found in pulmonary vascular smooth muscle cells and mediate smooth muscle contraction and the proliferation of smooth muscle cells and fibroblasts, while ETB receptors are expressed in endothelial cells (ETB1 receptors) and smooth muscle cells (ETB2 receptors) and cause either relaxation or contraction, respectively [2,3,4]. Since the pulmonary vascular bed is complex in terms of regional differences in both structure and function, it is important to know about localization and distribution of ET-1 and ET receptors. Although it is known that ET-1 is expressed in various cells including endothelial cells, epithelial cells, smooth muscle cells, and tissue macrophages in the lung [2,5,6], there are few studies showing the distribution of ET-1 and ECE expression along the axial pathways of the pulmonary artery.The over-expression of the messenger ribonucleic acid (mRNA) for ET-1, ETA and ETB receptors, and the overproduction of the ET-1 peptide in whole lung have been demonstrated in an experimental model of hypoxic pulmonary hypertension [6 -11]. Furthermore, blocking ETA receptors with selective antagonists attenuates the rise in pulmonary arte...

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“…(Vos et al, 1999), Kupffer cells (Mustafa et al, 1999) and endothelial cells (Laskin et al, 1994) produce NO that plays a dual role, being cytoprotective and cytotoxic (Li and Billiar, 1999;Laskin et al, 2001). The small amount of NO produced by endothelial NOS (eNOS) acts to maintain homeostasis and has a cytoprotective effect (Albrecht et al, 2003), whereas excessive NO formation by iNOS that is induced by cytokines (Nakayama et al, 1994) and LPS (Zhang et al, 2000) in hepatocytes or Kkupffer cells, exerts cytotoxic actions via lipid peroxidation (Shibuki et al, 2000), activation of poly(ADP-ribose) polymerase (Khandoga et al, 2002), apoptosis (Lin et al, 1999;Zhuang and Simon, 2000) and nitration of tyrosine residues (Haddad et al, 1994;Demiryurek et al, 2000). The present study demonstrated that a toxic dose of acetaminophen produced accumulation of NOx in the plasma, in addition to increased ALT/AST levels and extensive liver necrosis.…”

Section: Discussionmentioning

confidence: 99%

Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced hepatotoxicity in the rat

et al. 2003

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Accumulation of Nitrotyrosine Correlates with Endothelial NO Synthase in Pulmonary Resistance Arteries During Chronic Hypoxia in the Rat

Cited by 27 publications

References 27 publications

Is endothelial-nitric-oxide-synthase-derived nitric oxide involved in cardiac hypoxia/reoxygenation-related damage?

Is endothelial-nitric-oxide-synthase-derived nitric oxide involved in cardiac hypoxia/reoxygenation-related damage?

Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery

Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced hepatotoxicity in the rat

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