Nitric Oxide Facilitates Nicotine Absorption During Cigarette Smoking

一氧化氮促进吸烟过程中尼古丁的吸收

• 批准号: 9342752
• 负责人: Marc N Potenza
• 金额: $ 20.94万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9342752
• 关键词: Abstinence; Air; Airway Resistance; Blood specimen; Breathing; Cessation of life; Chemicals; Chronic; Chronic Obstructive Airway Disease; Cigarette; Congresses; Data; Dilator; Excision; Exhibits; Financial compensation; Foundations; Gases; Goals; Impairment; Inflammation Process; Knowledge; Lung; Mainstreaming; Manufacturer Name; Measurement; Measures; Nicotine; Nitrates; Nitric Oxide; Participant; Patient Self-Report; Perfusion; Plasma; Production; Property; Public Health; Pulmonary Hypertension; Pulmonary alveolar structure; Pulmonary vessels; Questionnaires; Recruitment Activity; Reporting; Resistance; Role; Signal Transduction; Smoke; Smoker; Smoking; System; Tars; Testing; Tobacco; Tobacco Use Disorder; absorption; blood perfusion; cigarette smoking; cigarette smoking; craving; negative affect; novel; public health relevance; pulmonary function; tobacco control

 DESCRIPTION (provided by applicant): Cigarette smoking is the leading cause of preventable death in the USA. In 2009, Congress passed the Tobacco Control Act and authorized the FDA to regulate cigarette ingredients to reduce their harm to the public. Therefore, knowledge of factors contributing to the addictive properties of cigarette smoking is urgently needed. The aim of the proposed project is to test the hypothesis that nitric oxide (NO) in cigarette smoke enhances the addictive properties of cigarette smoking by facilitating nicotine inhalation and absorption. NO is an endogenous signaling gas and a powerful dilator of airways and pulmonary vessels, and important for normal pulmonary function. Chronic smoking reduces NO production, induces an inflammation process in the pulmonary system, increases resistance of airways and pulmonary vessels, and may finally result in chronic obstructive pulmonary disease (COPD) and pulmonary hypertension. Inhaled cigarette smoke contains a high level of NO which may increase inhalation volume and pulmonary perfusion and air exchange by dilating airways and pulmonary vessels and reducing their resistance, thus facilitating nicotine inhalation and absorption, especially in chronic smokers with impaired pulmonary function. Relevant to this potential role of NO, cigarette manufacturers increased the NO in smoke by increasing nitrate, a main precursor of NO, in cigarettes, even though they reduced nicotine and tar during the same period from the 1950s-1990s. The increased NO may contribute to the so-called smoking compensation; i.e., tobacco-dependent smokers inhale deeper when smoking nicotine-reduced cigarettes relative to regular cigarettes. To test whether NO facilitates nicotine absorption, we will ask tobacco-dependent smokers to participate in two smoking sessions on two different days after overnight abstinence. Smokers will smoke a regular cigarette through a filter during each study session. The filter will remove NO from mainstream smoke during one session (i.e., real filter session (RFS)) but will not remove NO during the other session (i.e., dummy filter session (DFS)). Blood samples for assessing plasma nicotine levels will be acquired both before and after smoking during each session. Compared with the RFS, a significantly greater increase in plasma nicotine levels after smoking relative to before smoking in the DFS will support our hypothesis that NO facilitates nicotine absorption during cigarette smoking. We will acquire measures on craving, negative affect, and smoking effects during each session for comparing subjective effects of smoking during the two sessions. Positive findings from the proposed study will provide a foundation for subsequent studies assessing more fully a role for NO in tobacco-use disorder. The goal of these studies is to generate data for the FDA to decide whether and how to regulate NO and/or its precursors (e.g., nitrate) in cigarettes to promote public health by reducing the addictive properties of cigarette smoking.

 描述（由适用提供）：吸烟是美国可预防死亡的主要原因。 2009年，国会通过了《烟草控制法》，并授权FDA规范香烟罪犯以减少对公众的伤害。因此，迫切需要了解有助于吸烟的其他特性的因素。拟议项目的目的是检验以下假设：烟烟中的一氧化氮（NO）通过支持尼古丁事故和痛苦来增强吸烟的添加特性。否是内源性信号气体和气道和肺腔的强大扩张器，对于正常的肺功能很重要。慢性吸烟不会降低没有产生的生产，诱导肺部系统的注射过程，增加气道和肺壁的耐药性，最终可能导致慢性阻塞性肺部疾病（COPD）和肺动脉高压。吸入的香烟烟雾含有高水平的NO水平，通过扩张气道和肺动脉毒液并降低其耐药性，从而增加吸入量，肺部灌注和空气交换，从而产生尼古丁事故和滥用，尤其是在患有肺功能受损的慢性吸烟者中。与NO的潜在作用相关的是，香烟制造商通过增加硝酸盐的烟雾来增加NO烟雾，即硝酸盐是NO，香烟的主要先驱，即使他们在1950年代至1990年代同期减少了尼古丁和焦油。不增加的可能会导致所谓的吸烟补偿；即，相对于常规香烟，吸烟减少香烟时，依赖烟草的吸烟者会更深。为了测试是否没有收藏尼古丁滥用，我们会要求依赖烟草的吸烟者在过夜禁欲后的两个不同的日子参加两次吸烟。在每个研究期间，吸烟者将通过过滤器吸烟。过滤器将在一个会话（即真实的过滤器会话（RFS））中删除主流烟雾中的否，但在另一个会话期间不会删除否（即虚拟过滤器会话（DFS））。每次吸烟期间和之后，将获取用于评估血浆尼古丁水平的血液样本。与RF相比，吸烟后与DFS吸烟之前吸烟后血浆尼古丁水平的增加将支持我们的假设，即吸烟期间没有收藏夹尼古丁的受苦。我们将在每次会议期间就渴望，负面影响和吸烟效应采取措施，以比较两次会议期间吸烟的主观影响。拟议研究的积极发现将为随后的研究提供基础，以更全面地评估NO在烟草使用障碍中的作用。这些研究的目的是为FDA生成数据，以决定是否以及如何调节香烟中的NO和/或其前体（例如硝酸盐），以通过减少吸烟的其他特性来促进公共卫生。