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产生的烟雾对血管内皮血管扩张功能的直接有害影响是否与已知的暴露于烟草烟雾中的相同。围绕吸食大麻最普遍但又未经证实的公众信念之一是，与烟草的影响相比，大麻对吸烟者和旁观者的影响都是良性的。我们和其他人已经证明，暴露在烟草SHS中30分钟会导致人类和大鼠的血管扩张功能严重受损，这是通过超声测量动脉血流介导的血管扩张(FMD)来确定的，动脉血流介导的血管扩张(FMD)是衡量内皮健康的指标。这个实验室开发了一种活体大鼠口蹄疫系统，我们正在用它来研究烟草SHS的有害影响。我们将使用这个大鼠系统来测量大麻SHS对具有非常相似基因和生活方式的多个人的影响，并避免与人类接触这种受控物质相关的法律问题。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。我们推测，接触烟熏干烟叶，无论是烟草还是大麻，无论是否含有大麻！S精神活性成分，都会导致血管功能受损。这种情况的证明将产生反驳公众的普遍误解，即环境中暴露于大麻烟雾相对无害的误解。因为大麻！S越来越多地用于医疗目的，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，不吸食大麻的人在各种情况下仍然暴露在大麻的二手烟中，了解环境暴露于这种烟雾对公众健康的影响是很重要的。首先，我们将确定暴露于高水平和低水平大麻SHS的大鼠的FMD是否受损，暴露时间从30分钟到30秒不等，与烟草SHS和其他对照组的影响相比较。然后，我们将确定暴露于大麻主流烟雾或SHS的大鼠血清是否降低培养的内皮细胞的eNOS活性和NO产生。

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.