Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II.
Inhalation exposure to fine concentrated ambient particles (CAPs) increases cardiac oxidants by mechanisms involving modulation of the sympathovagal tone on the heart. Angiotensin-II is a potent vasoconstrictor and a sympatho-excitatory peptide involved in the regulation of blood pressure. We hypothesized that increases in angiotensin-II after fine particulate matter (PM) exposure could be involved in the development of cardiac oxidative stress. Adult rats were treated with an angiotensin-converting enzyme (ACE) inhibitor (benazepril), or an angiotensin receptor blocker (ARB; valsartan) before exposure to fine PM aerosols or filtered air. Exposures were carried out for 5 hours in the chamber of the Harvard fine particle concentrator (fine PM mass concentration: 440 +/- 80 microg/m(3)). At the end of the exposure the animals were tested for in situ chemiluminescence (CL) of the heart, thiobarbituric acid reactive substances (TBARS) and for plasma levels of angiotensin-II. Also, continuous electrocardiogram (ECG) measurements were collected on a subgroup of exposed animals. PM exposure was associated with statistically significant increases in plasma angiotensin concentrations. Pre-treatment with the ACE inhibitor effectively lowered angiotensin concentration, whereas ARB treatment led to increases in angiotensin above the PM-only level. PM exposure also led to significant increases in heart oxidative stress (CL, TBARS), and a shortening of the T-end to T-peak interval on the ECG that were prevented by treatment with both the ACE inhibitor and ARB. These results show that ambient fine particles can increase plasma levels of angiotensin-II and suggest a role of the renin-angiotensin system in the development of particle-related acute cardiac events.
Ghelfi
Elisa
E
Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Wellenius
Gregory A
GA
Lawrence
Joy
J
Millet
Emil
E
Gonzalez-Flecha
Beatriz
B
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D004562:Electrocardiography / Q000187:drug effects / Q000379:methods; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D019570:Inhalation Exposure / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D010316:Particle Size; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D052638:Particulate Matter; D000804:Angiotensin II