Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors

Sarah Robertson; Ashleigh L. Thomson; Rod Carter; Holly R. Stott; Catherine A. Shaw; Patrick W.F. Hadoke; David E. Newby; Mark R. Miller; Gillian A. Gray

doi:10.1186/1743-8977-11-12

Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors

Sarah Robertson, Ashleigh L. Thomson, Rod Carter, Holly R. Stott, Catherine A. Shaw, Patrick W.F. Hadoke, David E. Newby, Mark R. Miller, Gillian A. Gray^*

^*Corresponding author for this work

HP: Head Of Department EHE

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

Abstract

Background: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.Methods & Results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β₁ adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.Conclusions: Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

Original language	English
Article number	12
Pages (from-to)	1-10
Number of pages	10
Journal	Particle and Fibre Toxicology
Volume	11
Issue number	1
DOIs	https://doi.org/10.1186/1743-8977-11-12
Publication status	Published - Feb 2014

Bibliographical note

Funding Information:
This study was funded through grants from the British Heart Foundation (RG/05/003, PG/10/042/28388, CH09/002 to DEN; and a 4-year British Heart Foundation PhD Studentship to SR (FS/07/063). We also acknowledge the support of the British Heart Foundation Centre of Research Excellence (CoRE) award. Thanks to Ian Dransfield, Rodger Duffin, Steven McLean (Centre for Inflammation Research & Centre for Cardiovascular Sciences, University of Edinburgh) for additional technical assistance and helpful discussion.

Keywords

(3-10) air pollution
Ischemia/reperfusion injury
Sympathetic nervous system
Vanilloid receptor

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10.1186/1743-8977-11-12

Cite this

Robertson, S., Thomson, A. L., Carter, R., Stott, H. R., Shaw, C. A., Hadoke, P. W. F., Newby, D. E., Miller, M. R., & Gray, G. A. (2014). Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors. Particle and Fibre Toxicology, 11(1), 1-10. [12]. https://doi.org/10.1186/1743-8977-11-12

Robertson, Sarah ; Thomson, Ashleigh L. ; Carter, Rod ; Stott, Holly R. ; Shaw, Catherine A. ; Hadoke, Patrick W.F. ; Newby, David E. ; Miller, Mark R. ; Gray, Gillian A. / Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors. In: Particle and Fibre Toxicology. 2014 ; Vol. 11, No. 1. pp. 1-10.

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title = "Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors",

abstract = "Background: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.Methods & Results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.Conclusions: Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.",

keywords = "(3-10) air pollution, Ischemia/reperfusion injury, Sympathetic nervous system, Vanilloid receptor",

author = "Sarah Robertson and Thomson, {Ashleigh L.} and Rod Carter and Stott, {Holly R.} and Shaw, {Catherine A.} and Hadoke, {Patrick W.F.} and Newby, {David E.} and Miller, {Mark R.} and Gray, {Gillian A.}",

note = "Funding Information: This study was funded through grants from the British Heart Foundation (RG/05/003, PG/10/042/28388, CH09/002 to DEN; and a 4-year British Heart Foundation PhD Studentship to SR (FS/07/063). We also acknowledge the support of the British Heart Foundation Centre of Research Excellence (CoRE) award. Thanks to Ian Dransfield, Rodger Duffin, Steven McLean (Centre for Inflammation Research & Centre for Cardiovascular Sciences, University of Edinburgh) for additional technical assistance and helpful discussion.",

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language = "English",

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Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors. / Robertson, Sarah; Thomson, Ashleigh L.; Carter, Rod; Stott, Holly R.; Shaw, Catherine A.; Hadoke, Patrick W.F.; Newby, David E.; Miller, Mark R.; Gray, Gillian A.

In: Particle and Fibre Toxicology, Vol. 11, No. 1, 12, 02.2014, p. 1-10.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors

AU - Robertson, Sarah

AU - Thomson, Ashleigh L.

AU - Carter, Rod

AU - Stott, Holly R.

AU - Shaw, Catherine A.

AU - Hadoke, Patrick W.F.

AU - Newby, David E.

AU - Miller, Mark R.

AU - Gray, Gillian A.

N1 - Funding Information: This study was funded through grants from the British Heart Foundation (RG/05/003, PG/10/042/28388, CH09/002 to DEN; and a 4-year British Heart Foundation PhD Studentship to SR (FS/07/063). We also acknowledge the support of the British Heart Foundation Centre of Research Excellence (CoRE) award. Thanks to Ian Dransfield, Rodger Duffin, Steven McLean (Centre for Inflammation Research & Centre for Cardiovascular Sciences, University of Edinburgh) for additional technical assistance and helpful discussion.

PY - 2014/2

Y1 - 2014/2

N2 - Background: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.Methods & Results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.Conclusions: Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

AB - Background: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.Methods & Results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic β1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury.Conclusions: Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.

KW - (3-10) air pollution

KW - Ischemia/reperfusion injury

KW - Sympathetic nervous system

KW - Vanilloid receptor

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DO - 10.1186/1743-8977-11-12

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C2 - 24568236

AN - SCOPUS:84899478723

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JO - Particle and Fibre Toxicology

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SN - 1743-8977

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ER -

Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and β1 adrenoreceptors

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