Evaluation of harmful effects of cannabis smoke on vascular endothelial function

大麻烟雾对血管内皮功能有害影响的评价

• 批准号: 8174578
• 负责人: MATTHEW Lawrence SPRINGER
• 金额: $ 23.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8174578
• 关键词: Belief; Benign; Blood Vessels; California; Cannabis Smoking; Cardiovascular system; Cigarette; Endothelial Cells; Environmental Exposure; Environmental Tobacco Smoke; Enzymes; Evaluation; Exposure to; General Population; Genetic; Health; Human; Impairment; Individual; Laboratories; Legal; Life; Life Style; Mainstreaming; Marijuana; Marijuana Smoking; Measurement; Measures; Mediating; Nitric Oxide; Nitric Oxide Synthase; Passive Smoking; Production; Public Health; Rattus; Relative (related person); Serum; Smoke; Smoker; System; Time; Tobacco; Tobacco smoke; Ultrasonography; Vasodilation; human NOS3 protein; non-smoker

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.

描述（由申请人提供）： 我们将确定大麻香烟烟雾是否对血管内皮血管舒张功能具有与已知暴露于烟草烟雾所产生的相同的直接有害影响。 关于吸食大麻最普遍但未经证实的公众信念之一是，相对于烟草的影响，大麻对吸烟者和旁观者的影响是良性的。我们和其他人已经证明，接触烟草二手烟 30 分钟会导致人类和大鼠的血管舒张功能严重受损，这一点是通过动脉血流介导的血管舒张（FMD）（内皮健康指标）的超声测量来确定的。该实验室开发了活体大鼠 FMD 系统，我们用它来研究烟草二手烟的有害影响。我们将使用这个老鼠系统来测量大麻 SHS 对具有非常相似的遗传和生活方式的多个个体的影响，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二手烟是否会降低培养的内皮细胞中一氧化氮的产生。我们假设，接触阴燃干叶产生的烟雾，无论是烟草还是大麻，也无论是否存在大麻的精神活性成分，都会导致血管功能受损。证明这种情况的证明将有助于纠正公众的普遍误解，即环境中暴露于大麻烟雾相对无害。由于大麻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，即不吸食大麻的人仍然在各种情况下接触二手烟，因此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的大麻 SHS 的大鼠中，与烟草 SHS 和其他对照的影响相比，FMD 是否受到损害，暴露时间从 30 分钟到短暂的 30 秒不等。然后，我们将确定暴露于大麻主流烟雾或二手烟的大鼠的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产生的烟雾是否对心血管系统产生与已知的接触烟草二手烟造成的相同的直接有害影响。由于大麻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，即不吸食大麻的人仍然在各种情况下接触二手烟，因此了解环境暴露于这种烟雾对公共健康的影响非常重要。