Program Director/Principal Investigator (Last, First, Middle): Conklin, Daniel J., Ph.D. ABSTRACT Extensive epidemiological evidence suggests that exposure to vegetation and residential proximity to greenspaces lowers the risk of all-cause mortality, cardiovascular disease, anxiety, depression and aggression. Although it has been suggested that urban greenspaces exert their beneficial effects by removing air pollutants and promoting physical activity, plants emit biogenic volatile organic chemicals (BVOCs), which by eliciting beneficial cardiovascular and neurological effects could mediate the salutary effects of vegetation. Vegetation is a major underappreciated domain of the natural environment that has received limited interest. Exposure to greenspace within the natural environment has been linked to improvements in cardiovascular health. We propose that plant-derived BVOCs including pinenes, limonene, and citronellol stimulate distinct signaling pathways, in part, by activating the transient receptor potential ankyrin-1 (TRPA1) channel on cardiovascular targets. In endothelial cells, for example, activation of TRPA1 releases nitric oxide that lowers blood pressure, improves cardiovascular function and tamps down inflammation and thrombosis leading to an overall decrease in cardiovascular disease risk. Completion of this project will rigorously establish beneficial cardiovascular effects of inhaled BVOCs that are prevalent in human environments. Moreover, our studies will provide a first test of hypothesis that beneficial effects of inhaled BVOCs are mediated, in part, by TRPA1. These preclinical studies may also lead to the development of biomarkers of exposure to greenness, which likely will be useful in clinical evaluation of the potential therapeutic use of greenness (e.g., planting trees) to decrease CVD risk in human populations. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page