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Intranasal benzo[a]pyrene alters circadian blood pressure patterns and causes lung inflammation in rats

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Abstract

Polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BaP), are environmental contaminants formed during organic material combustion (e.g. burning fossil fuels and cigarette smoke). BaP toxicity is mediated, in part, by activation of the aryl hydrocarbon receptor and formation of reactive metabolites, both of which lead to increased oxidative stress. Since air pollution and cigarette smoking are known to increase cardiovascular disease in humans, the objective of this study was to determine the effects of 7-day intranasal BaP exposure on circadian blood pressure patterns, arterial stiffness, and possible sources of oxidative stress in radiotelemetry-implanted rats. Arterial pulse wave dP/dt was used an indicator of arterial stiffness and was compared to both functional (nitric oxide production and bioactivity, endothelin-1 levels) and structural (wall thickness) features of the arterial wall. In addition, histology of lung, heart, and liver were examined as well as pulmonary and hepatic cytochrome P450 1A1 (CYP1A1) activity. BaP exposure altered the circadian pattern of blood pressure, with a reduction in the normal dipping pattern during sleep. This was associated with increased neutrophil recruitment in the lungs of BaP-exposed rats. In contrast, BaP had no effect on cardiovascular tissue histology, arterial stiffness, oxidative stress or lung and liver CYP1A1 activity. Thus, the current study does not support the hypothesis that BaP reactive metabolites increase oxidative stress leading to reduced vascular NO bioactivity and increased blood pressure. Instead, the current study suggests that inflammation, detected only in the lung, is associated with altered circadian rhythm of blood pressure.

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Acknowledgments

The authors would like to thank Saskatchewan Health Research Foundation for providing funds for this research. Thanks also to the Natural Sciences and Engineering Research Council for scholarship support for N. Gentner (PGS-M) and an equipment grant for the telemetry system (NSERC RTI).

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The authors do not have any conflicts of interest to declare.

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  1. Toxicology Graduate Program, University of Saskatchewan, Saskatoon, SK, Canada

    Nicole J. Gentner & Lynn P. Weber

  2. Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada

    Lynn P. Weber

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  1. Nicole J. Gentner
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Correspondence to Lynn P. Weber.

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Gentner, N.J., Weber, L.P. Intranasal benzo[a]pyrene alters circadian blood pressure patterns and causes lung inflammation in rats. Arch Toxicol 85, 337–346 (2011). https://doi.org/10.1007/s00204-010-0589-6

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