Evaluation of harmful effects of cannabis smoke on vascular endothelial function

描述（由申请人提供）： 我们将确定大麻香烟的烟雾是否对血管内皮舒张功能具有与已知暴露于烟草烟雾中的有害作用相同的直接有害作用。 围绕吸食大麻的最普遍但未经证实的公众信念之一是，它对吸烟者和旁观者的影响相对于烟草的影响是良性的。我们和其他人已经表明，暴露于烟草SHS 30分钟会导致人类和大鼠血管舒张功能的实质性损害，这是通过动脉血流介导的血管舒张（FMD）的超声测量（一种内皮健康的测量）确定的。本实验室开发了一种活体大鼠FMD系统，我们正在使用该系统研究烟草SHS的有害影响。我们将使用这种大鼠系统，既能够测量大麻SHS在具有非常相似的遗传学和生活方式的多个个体中的影响，又能够避免与人类接触这种受控物质相关的法律的问题。我们还将确定暴露于大麻主流烟雾或SHS是否会降低培养的内皮细胞中NO的产生。我们假设，暴露于冒烟的干叶，无论是烟草或大麻，无论大麻的存在！的精神活性成分，导致血管功能受损。这种情况的证明将产生对抗公众普遍误解的影响，即环境暴露于大麻烟雾相对无害。因为大麻！随着大麻用于医疗目的的日益增加，以及加州等地正在努力使大麻合法化，更不用说不可否认的事实，即大麻非吸烟者在各种情况下仍然暴露在二手烟中，了解环境暴露于这种烟雾对公共健康的影响非常重要。 首先，我们将确定暴露于高水平和低水平大麻SHS的大鼠中FMD是否受损，暴露时间从30分钟到短暂的30秒暴露，与烟草SHS和其他对照的影响相比。然后，我们将确定暴露于大麻主流烟雾或SHS的大鼠血清是否会降低培养的内皮细胞中的eNOS活性和NO产生。 公共卫生相关性： 许多普通公众，甚至那些避免吸烟的人，都认为接触大麻烟雾相对无害。我们将确定大麻香烟的烟雾是否对心血管系统有相同的直接有害影响，因为那些已知的暴露于烟草二手烟。因为大麻！随着大麻用于医疗目的的日益增加，以及加州等地正在努力使大麻合法化，更不用说大麻非吸烟者在各种情况下仍然暴露在二手烟中这一不可否认的事实，了解环境暴露于这种烟雾对公共健康的影响是很重要的。

DESCRIPTION (provided by applicant): We will determine whether smoke from marijuana cigarettes has the same immediate deleterious effects on vascular endothelial vasodilatory function as those that are known to occur from exposure to tobacco smoke. One of the most pervasive, yet unsubstantiated, public beliefs surrounding marijuana smoking is that its effects on its smokers and bystanders alike are benign relative to the effects of tobacco. We and others have shown that exposure to tobacco SHS for 30 minutes causes substantial impairment of vasodilatory function in both humans and rats, as determined by ultrasound measurement of arterial flow-mediated vasodilation (FMD), a measure of endothelial health. This laboratory has developed a living rat FMD system that we are using to study the harmful effects of tobacco SHS. We will use this rat system both to be able to measure the effects of marijuana SHS in multiple individuals with very similar genetics and lifestyle, and to avoid the legal issues associated with exposing humans to this controlled substance. We wil also determine if exposure to marijuana mainstream smoke or SHS lowers NO production in cultured endothelial cells. We hypothesize that exposure to smoke from smoldering dried leaves, whether tobaco or marijuana and regardless of the presence of marijuana!s psychoactive component, causes impairment of vascular function. The demonstration that this is the case would have the impact of countering the common public misperception that environmental exposure to marijuana smoke is relatively harmless. Because of marijuana!s increasing use for medicinal purposes, and efforts underway in places like California to legalize marijuana, not to mention the undeniable fact that marijuana non-smokers are still exposed to its secondhand smoke in various situations, it is important to understand the public health effects of environmental exposure to this smoke. First, we will determine whether FMD is impaired in rats exposed to high and low levels of marijuana SHS, for exposure times ranging from 30 minutes down to a brief 30-second exposure, compared to the effects of tobacco SHS and other controls. Then, we will determine whether serum from rats that have been exposed to marijuana mainstream smoke or SHS lowers eNOS activity and NO production in cultured endothelial cells. PUBLIC HEALTH RELEVANCE: Many in the general public, even those who avoid tobacco smoke, believe that exposure to marijuana smoke is relatively harmless. We will determine whether smoke from marijuana cigarettes has the same immediate harmful efects on the cardiovascular system as those that are known to occur from exposure to tobacco secondhand smoke. Because of marijuana!s increasing use for medicinal purposes, and efforts underway in places like California to legalize marijuana, not to mention the undeniable fact that marijuana non- smokers are still exposed to its secondhand smoke in various situations, it is important to understand the public health effects of environmental exposure to this smoke.