title: Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated ambient particles are mediated by TRP-dependent pulmonary reflexes.
abstract: Previous studies suggest that, through the stimulation of pulmonary nervous endings, ambient particles modulate the autonomic tone on the heart leading to cardiac oxidant stress and dysfunction. In this paper we investigated the effect of blockade of vanilloid receptor 1 (Transient Receptor Potential Vanilloid Receptor 1 [TRPV1]) on concentrated ambient particles (CAPs)-induced cardiac oxidative stress and dysfunction in a rat model of inhalation exposure. Capsazepine (CPZ), a selective antagonist of TRPV1, was given ip or as an aerosol immediately before exposure to CAPs. Control and CPZ-treated rats were exposed to filtered air or CAPs aerosols for 5 h using the Harvard Ambient Particle Concentrator (mean PM(2.5) mass concentration: 218 +/- 23 mug/m(3)). At the end of the exposure we measured cardiac oxidative stress (in situ chemiluminescence [CL]), lipid peroxidation (thiobarbituric acid reactive substances [TBARS]), and tissue edema. Cardiac function was monitored throughout the exposure. CPZ (ip or aerosol) decreased CAPs-induced CL, lipid TBARS, and edema in the heart, indicating that blocking TRP receptors, systemically or locally, decreases heart CL. CAPs exposure led to significant decreases in heart rate (CAPs 350 +/- 32 bpm, control: 370 +/- 29), and in the length of the QT, RT, Pdur and Tpe intervals. These changes were observable immediately upon exposure and were maintained throughout the 5 h of CAPs inhalation. Changes in cardiac rhythm and electrocardiogram morphology were prevented by CPZ. These data suggest that current abnormalities in CAPs-exposed rats alter the action potentials leading to changes in conduction velocity and ventricular repolarization, and that triggering of TRPV1-mediated autonomic reflexes in the lung is essential for the observed changes in cardiac rhythms.
authors.affiliation: Harvard School of Public Health, Department of Environmental Health, Boston, Massachusetts, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ghelfi
authors.forename: Claudia Ramos
authors.initials: CR
authors.lastname: Rhoden
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wellenius
authors.forename: Joy
authors.initials: J
authors.lastname: Lawrence
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gonzalez-Flecha
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004487:Edema; D004489:Edema, Cardiac / Q000139:chemically induced / Q000473:pathology; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D019570:Inhalation Exposure; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C071423:capsazepine; D002211:Capsaicin