Christina Lee Brown Envirome Institute, University of Louisville, Louisville, Kentucky, United States.
Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky, United States.
Am J Physiol Heart Circ Physiol. 2023 Dec 1;325(6):H1446-H1460. doi: 10.1152/ajpheart.00380.2023. Epub 2023 Oct 27.
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 α-pinene that could elicit beneficial cardiovascular effects. To explore the role of α-pinene more directly, we studied the metabolism and the vascular effects of α-pinene. We found that exposure of mice to α-pinene (1 ppm, 6 h) generated two phase I oxidation metabolites, - and -verbenol [(1,2,5)-verbenol and (1 ,2,5)-verbenol)] and myrtenol [(1,5)-(+)-myrtenol] that were identified in urine by GC-MS. Precontracted naïve murine male and female aorta and superior mesenteric artery (SMA) were relaxed robustly (60% tension reduction) by increasing concentrations of α-pinene, myrtenol, and verbenol to 0.3 mM, whereas 1 mM α-pinene was vasotoxic. The SMA was six times more sensitive than the aorta to α-pinene. Both myrtenol and verbenol were equally potent and efficacious as parent α-pinene in male and female SMA. The sensitive portion of the α-pinene-, myrtenol-, and verbenol-induced relaxations in male SMA was mediated by ) endothelium, ) eNOS-derived NO, and ) guanylyl cyclase (GC) activity. Moreover, α-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) α-pinene (or its metabolites) augments NO release to mediate the cardiovascular benefits of exposure to greenness. A common plant-derived biogenic volatile organic compound, α-pinene, and two of its metabolites, myrtenol and verbenol, stimulate vasorelaxation in murine superior mesenteric artery. Both α-pinene- and its metabolites induce vasorelaxation by activation of the endothelium, nitric oxide, and guanylyl cyclase. α-Pinene also activates the transient receptor potential ankyrin-1. Positive associations between greenness exposure and human cardiovascular health may be a result of the vascular action of α-pinene and its metabolites, a novel consideration.
流行病学证据表明，居住在绿地附近与全因和心血管死亡率降低有关；然而，这种联系的机制尚不清楚。植物会释放出生物源挥发性有机化合物，如α-蒎烯，它可能会产生有益的心血管效应。为了更直接地探索α-蒎烯的作用，我们研究了它的代谢和血管作用。我们发现，将小鼠暴露于α-蒎烯（1 ppm，6 小时）会产生两种 I 相氧化代谢物，即β-和γ-马鞭烯醇[（1,2,5）-马鞭烯醇和（1,2,5）-马鞭烯醇]和桃金娘烯醇[（1,5）-（+）-桃金娘烯醇]，这些代谢物通过 GC-MS 在尿液中被鉴定出来。浓度增加到 0.3 mM 时，α-蒎烯、桃金娘烯醇和马鞭烯醇可使未经预处理的雄性和雌性小鼠主动脉和肠系膜上动脉（SMA）显著松弛（张力降低 60%），而 1 mM 的α-蒎烯则具有血管毒性。SMA 对α-蒎烯的敏感性是主动脉的六倍。在雄性 SMA 中，桃金娘烯醇和马鞭烯醇与亲代α-蒎烯一样有效和有效。α-蒎烯、桃金娘烯醇和马鞭烯醇诱导的雄性 SMA 松弛的敏感部分是通过内皮细胞、eNOS 衍生的 NO 和鸟苷酸环化酶（GC）活性介导的。此外，α-蒎烯激活瞬时受体电位锚蛋白-1（TRPA1）通道，而代谢物则没有。内皮细胞衍生的 NO 调节血流、血压和血栓形成，因此吸入（和摄入）α-蒎烯（或其代谢物）可能会增加 NO 的释放，从而介导暴露于绿色环境对心血管的益处。一种常见的植物源性生物源挥发性有机化合物，α-蒎烯，及其两种代谢物，桃金娘烯醇和马鞭烯醇，可刺激小鼠肠系膜上动脉的血管舒张。α-蒎烯及其代谢物均通过激活内皮细胞、一氧化氮和鸟苷酸环化酶来诱导血管舒张。α-蒎烯还激活瞬时受体电位锚蛋白-1。绿色环境暴露与人类心血管健康之间的正相关关系可能是α-蒎烯及其代谢物的血管作用的结果，这是一个新的考虑因素。
