Impairment of coronary endothelial cell ET_B receptor function after short-term inhalation exposure to whole diesel emissions

Abstract

Air pollutant levels positively correlate with increases in both acute and chronic cardiovascular disease. The pollutant diesel exhaust (DE) increases endothelin (ET) levels, suggesting that this peptide may contribute to DE-induced cardiovascular disease. We hypothesized that acute exposure to DE also enhances ET-1-mediated coronary artery constrictor sensitivity. Constrictor responses to KCl, U-46619, and ET-1 were recorded by videomicroscopy in pressurized intraseptal coronary arteries from rats exposed for 5 h to DE (300 microg/m(3)) or filtered air (Air). ET-1 constriction was augmented in arteries from DE-exposed rats. Nitric oxide synthase (NOS) inhibition [N(omega)-nitro-L-arginine (L-NNA), 100 microM] and endothelium inactivation augmented ET-1 responses in arteries from Air but not DE rats so that after either treatment responses were not different between groups. DE exposure did not affect KCl and U-46619 constrictor responses, while NOS inhibition augmented KCl constriction equally in both groups. Thus basal NOS activity does not appear to be affected by DE exposure. The endothelin type B (ET(B)) receptor antagonist BQ-788 (10 microM) inhibited ET-1 constriction in DE but not Air arteries, and constriction in the presence of the antagonist was not different between groups. Cytokine levels were not different in plasma from DE and AIR rats, suggesting that acute exposure to DE does not cause an immediate inflammatory response. In summary, a 5-h DE exposure selectively increases constrictor sensitivity to ET-1. This augmentation is endothelium-, NOS-, and ET(B) receptor dependent. These data suggest that DE exposure diminishes ET(B) receptor activation of endothelial NOS and augments ET(B)-dependent vasoconstriction. This augmented coronary vasoreactivity to ET-1 after DE, coupled with previous reports that DE induces production of ET-1, suggests that ET-1 may contribute to the increased incidence of cardiac events during acute increases in air pollution levels.

Particulate Matter Air Pollution and Cardiovascular Disease

“…In separate experiments, diesel exhaust exposure to rats for 5 hours augmented ET-induced vasoconstriction, potentially via a blunting of ET-B-induced nitric oxide release. 365 The findings suggest that exposure to a fresh mixture of PM, gases, and vapors may play a role in rapidly triggering atherosclerotic plaque vulnerability via ROS and ET-dependent upregulation of MMP levels.…”

Environmental factors in cardiovascular disease

“…72 Inhaled particles might also interact with nociceptive or noradrenergic receptors to stimulate the sympathetic nervous system, raising circulating levels of vasoconstrictors, elevating blood pressure, and decreasing blood flow to the heart. 114 Neurogenic inflammation and the release of vasoactive mediators such as angiotensin II and en dothelin-1 can subsequently induce the expression of adhesion molecules, cytokines, and profibrotic mediators, and generate reactive oxygen species (ROS). 115 These effects can induce systemic inflammation, trigger plaque disruption and occlusion, or precipitate ischaemia-associated arrhythmia and myocardial damage.…”

Spatial and seasonal distribution of aerosol chemical components in New York City: (2) Road dust and other tracers of traffic-generated air pollution

“…In both studies, they were able to produce acute pulmonary changes and increases in blood fibrinogen with both concentrated ambient particles (CAPs) and concentrated DEP, but it took far higher concentrations of DEP than CAPs to do so. Others (USEPA, 2002;Hesterberg et al, 2005;Mills et al, 2005Mills et al, , 2007Li et al, 2007;Spira-Cohen et al, 2008;Cherng et al, 2009;Quan et al, 2010) have shown associations between human exposure to DEP and oxidative stress, proinflammatory cytokines, asthma aggravation, atherosclerotic disease, and a large number of other important health end points. In order words, exposure to DEP is widely understood to have significant effects on human health.…”