Epidemiological studies have linked levels of particulate matter (PM) in ambient air to cardiovascular mortality and hospitalizations for myocardial infarction (MI) and stroke. Thrombus formation plays a primary role in potentiating acute cardiovascular events, and this study was undertaken to determine whether pulmonary exposure to PM alters hemostasis. PM was collected from the Chapel Hill, NC airshed and was administered to mice by intratracheal instillation at a dose previously shown to exacerbate myocardial ischemia-reperfusion injury. Twenty-four hours after exposure, an increase occurred in the number of circulating platelets and plasma concentrations of fibrinogen and soluble P-selectin. The concentration of tissue factor pathway inhibitor (TFPI) in plasma was decreased, whereas the plasma concentration of plasminogen activator inhibitor (PAI-1) was increased. Consistent with these observations, bleeding time from a tail-tip transection was shortened. These results provide evidence that PM exposure alters hemostasis in otherwise healthy animals and may thereby promote clot formation and impede clot resolution in susceptible individuals. The results also establish definite hemostatic endpoints that can be used to further investigate the effects of dose and particle characteristics on the toxicity of ambient particles.

The vascular activity of scutellarin (SCU), a flavonoid isolated from a Chinese traditional medicinal plant, was investigated in isolated thoracic aortic rings of mice. SCU-induced dose-dependent relaxation of phenylephrine (1 microM) stimulated contractions. This relaxation was reduced by endothelium removal, significantly reduced by both the nitric oxide synthase inhibitor (Nomega-nitro-L-arginine methylester, 300 microM) and slightly limited by the soluble guanylyl cyclase inhibitor (1 H-[1,2,4] oxidazolol [4,3-a] quinoxalin-1-one, 100 microM). The catalase inhibitor (3-amino-1,2,4-triazole, 50 mM) augmented the constriction and blocked the lowest SCU concentration relaxation, whereas catalase addition was without effect. Preincubation with 300 and 1000 microM SCU significantly suppressed the contractile dose-response to phenylephrine, causing both a significant rise in half maximal effective concentration and a decrease in the maximal developed force. Western blot analysis showed that SCU inhibition of contraction was independent of reductions in myosin light chain phosphorylation. These results suggested that SCU relaxation was predominantly endothelium dependent and likely involved the catalase-sensitive nitric oxide synthase signaling pathway, without loss of myosin phosphorylation. The potential clinical use of SCU may prove to be effective in increasing vasoreactivity, independently of smooth muscle contractile activity that is mediated by the 20-kDa myosin light chain phosphorylation.

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