Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II
Source: Inhalation Toxicology, Volume 22, Number 11, September 2010 , pp. 963-972(10)
Publisher: Informa Healthcare
Abstract: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 g/m3). 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.
Document Type: Research Article
Publication date: September 2010