The present data demonstrated that despite impaired relaxation in response to acetylcholine, the vasodilator response

PFT�� cost evoked by an NO donor was not changed by PM2.5 exposure, suggesting that smooth muscle responsiveness to NO was not modified by PM2.5. It is known that NOS activity inhibition with L-NAME is able to abolish acetylcholine-induced relaxation in rat pulmonary arteries, suggesting that NO is the pivotal endothelial derived factor in rat pulmonary arteries (Shahbazian et al., 2007). In addition, it was previously demonstrated that eNOS is the main isoform of NOS involved in the synthesis of NO in health pulmonary artery (Steudel et al., 1998). Thus, we investigated whether in vivo PM2.5 selleck chemicals llc exposure could modulate the protein expression of eNOS in pulmonary arteries. It was found that 2 weeks of PM2.5 exposure significantly reduced the eNOS protein content in pulmonary arteries. A previous

study from our group showed that long term exposure (45 days), but not an early exposure, to air pollution in São Paulo city is able to decrease eNOS protein expression detected by immunohistochemistry in pulmonary arterioles ( Matsumoto et al., 2010). However, eNOS expression and vascular reactivity of extralobar circulation were not evaluated in that study. Here, we demonstrated that there is a positive correlation between eNOS and maximal relaxation evoked by acetylcholine in extralobar pulmonary arteries and the arterial rings from PM2.5-exposed animals that show lower values of relaxation to acetylcholine and also less eNOS protein expression. Taken together, our data suggest for the first time that the endothelial dysfunction elicited by early PM2.5 exposure in healthy Interleukin-2 receptor rats is related to an impairment in the vasodilator effect of eNOS-derived NO in the pulmonary circulation. The animals here were daily exposure to concentrated PM2.5 at a level of 600 μg/m3 that represents a mean of 25 μg/m3 over 24 h. Considering that ambient annual concentration of PM2.5 in São Paulo city is 28 μg/m3 ( Miranda et al., 2012), the rodents were expose to

a PM2.5 concentration near the real environmental that São Paulo people are exposed. In addition to a reduction in NO synthesis, superoxide anions scavenge NO, reducing its bioavailability and thus contributing to endothelial dysfunction (Förstermann, 2010 and Grunfeld et al., 1995). The present results demonstrated for the first time that enhanced formation of superoxide anion was present in pulmonary arteries from animals exposed to 14 days of concentrated urban PM2.5, which could contribute to even more reduced endothelial-dependent relaxation evoked by acetylcholine. The enhanced superoxide anion generation in pulmonary arteries from PM2.5-exposed rats was confirmed by the effect of PEG-SOD incubation in reducing to control levels the fluorescent signal of hydroethidine.