First Author | Jin L | Year | 2023 |
Journal | Am J Physiol Heart Circ Physiol | Volume | 325 |
Issue | 6 | Pages | H1446-H1460 |
PubMed ID | 37889254 | Mgi Jnum | J:342469 |
Mgi Id | MGI:7545411 | Doi | 10.1152/ajpheart.00380.2023 |
Citation | Jin L, et al. (2023) Endothelial-dependent Relaxation of Alpha-Pinene and Two Metabolites, Myrtenol and Verbenol, in Isolated Murine Blood Vessels. Am J Physiol Heart Circ Physiol |
abstractText | Epidemiological evidence shows that residential proximity to greenspaces is associated with lower risk of all-cause and cardiovascular mortality; however, the mechanism(s) underlying this link remains unclear. Plants emit biogenic volatile organic compounds such as a-pinene that could elicit beneficial cardiovascular effects. To explore the role of a-pinene more directly, we studied the metabolism and the vascular effects of a-pinene. We found that exposure of mice to a-pinene (1 ppm, 6h) generated two Phase I oxidation metabolites, cis- and trans-verbenol [(1R,2R,5R)-verbenol and (1R,2S,5R)-verbenol)] and myrtenol ((1S,5R)-(+)-myrtenol) that were identified in urine by GC-MS. Precontracted naive murine male and female aorta and superior mesenteric artery (SMA) were relaxed robustly (60% tension reduction) by increasing concentrations of a-pinene, myrtenol, and verbenol to 0.3 mM, whereas 1 mM a-pinene was vasotoxic. The SMA was 6x more sensitive than the aorta to a-pinene. Both myrtenol and verbenol were equally potent and efficacious as parent a-pinene in male and female SMA. The sensitive portion of the a-pinene-, myrtenol-, and verbenol-induced relaxations in male SMA was mediated by: 1) endothelium; 2 eNOS-derived NO; and, 3) guanylyl cyclase (GC) activity. Moreover, a-pinene activated the transient receptor potential ankyrin-1 (TRPA1) channel whereas the metabolites did not. Endothelial-derived NO regulates blood flow, blood pressure, and thrombosis, and it is plausible that inhaled (and ingested) a-pinene (or its metabolites) augments NO release to mediate the cardiovascular benefits of exposure to greenness. |