Monocrotaline pyrrole induces pulmonary endothelial damage through binding to and release from erythrocytes in lung during venous blood reoxygenation
Monocrotaline has been widely used to establish an animal model of pulmonary hypertension, most frequently in rats. An important feature of this model resides in the selectivity of monocrotaline injury toward the pulmonary vascular endothelium versus the systemic vasculature when administrated at standard dosage. The toxic metabolite of monocrotaline, monocrotaline pyrrole, is transported by erythrocytes. This study aimed to reveal whether partial pressure of oxygen of blood determined the binding and release of monocrotaline pyrrole from erythrocytes in rats with one subcutaneous injection of monocrotatline at the standard dosage of 60 mg/kg. Our experiments demonstrated that monocrotaline pyrrole bound to and released from erythrocytes at the physiological levels of partial pressure of oxygen in venous and arterial blood, respectively, and then aggregated on pulmonary artery endothelial cells. Monocrotaline pyrrole-induced damage of endothelial cells was also dependent on partial pressure of oxygen. In conclusion, our results demonstrate the importance of oxygen partial pressure on monocrotaline pyrrole binding to erythrocytes and on aggregation and injury of pulmonary endothelial cells. We suggest that these mechanisms contribute to pulmonary selectivity of this toxic injury model of pulmonary hypertension.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:316 |
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| Enthalten in: |
American journal of physiology. Lung cellular and molecular physiology - 316(2019), 5 vom: 01. Mai, Seite L798-L809 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xiao, Rui [VerfasserIn] |
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| Links: |
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| Themen: |
23291-96-5 |
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| Anmerkungen: |
Date Completed 11.02.2020 Date Revised 30.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1152/ajplung.00279.2018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM294105166 |
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| 245 | 1 | 0 | |a Monocrotaline pyrrole induces pulmonary endothelial damage through binding to and release from erythrocytes in lung during venous blood reoxygenation |
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| 520 | |a Monocrotaline has been widely used to establish an animal model of pulmonary hypertension, most frequently in rats. An important feature of this model resides in the selectivity of monocrotaline injury toward the pulmonary vascular endothelium versus the systemic vasculature when administrated at standard dosage. The toxic metabolite of monocrotaline, monocrotaline pyrrole, is transported by erythrocytes. This study aimed to reveal whether partial pressure of oxygen of blood determined the binding and release of monocrotaline pyrrole from erythrocytes in rats with one subcutaneous injection of monocrotatline at the standard dosage of 60 mg/kg. Our experiments demonstrated that monocrotaline pyrrole bound to and released from erythrocytes at the physiological levels of partial pressure of oxygen in venous and arterial blood, respectively, and then aggregated on pulmonary artery endothelial cells. Monocrotaline pyrrole-induced damage of endothelial cells was also dependent on partial pressure of oxygen. In conclusion, our results demonstrate the importance of oxygen partial pressure on monocrotaline pyrrole binding to erythrocytes and on aggregation and injury of pulmonary endothelial cells. We suggest that these mechanisms contribute to pulmonary selectivity of this toxic injury model of pulmonary hypertension | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a endothelial injury | |
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| 700 | 1 | |a Zhu, Liping |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Yankai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiansha |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Jing, Zhi-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Dupuis, Jocelyn |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Shengquan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Qinghua |e verfasserin |4 aut | |
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