Intranasal benzo[a]pyrene alters circadian blood pressure patterns and causes lung inflammation in rats.
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.
Gentner
Nicole J
NJ
Toxicology Graduate Program, University of Saskatchewan, Saskatoon, SK, Canada.
Weber
Lynn P
LP
D000281:Administration, Intranasal; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002940:Circadian Rhythm / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects
D002274:Carcinogens, Environmental; D001564:Benzo(a)pyrene