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（由申请人提供）：吸烟是美国可预防死亡的主要原因。2009 年，国会通过了《烟草控制法案》，并授权 FDA 监管卷烟成分，以减少其对公众的危害。迫切需要研究香烟烟雾中的一氧化氮（NO）通过促进吸烟的成瘾性来增强吸烟的成瘾性。尼古丁吸入和吸收是一种内源性信号气体，是气道和肺血管的强大扩张剂，对正常肺功能很重要，长期吸烟会减少一氧化氮的产生，诱发肺系统炎症过程，增加气道和肺血管的阻力。 ，并最终可能导致慢性阻塞性肺病（COPD）和肺动脉高压。吸入香烟烟雾中含有高浓度的一氧化氮，它可能通过扩张气道和肺血管并减少吸入量、增加肺灌注和空气交换。尼古丁的抵抗力，从而促进尼古丁的吸入和吸收，特别是对于肺功能受损的长期吸烟者来说，与一氧化氮的这种潜在作用相关，卷烟制造商通过在香烟中增加硝酸盐（一氧化氮的主要前体）来增加烟雾中的一氧化氮，尽管它们。 20世纪50年代至90年代同期尼古丁和焦油的减少，NO的增加可能有助于所谓的吸烟补偿，即依赖烟草的吸烟者吸烟时吸入更深。为了测试 NO 是否促进尼古丁吸收，我们将要求吸烟者在隔夜戒烟后的两天内参加两次吸烟活动，吸烟者将在每次研究期间通过过滤嘴吸烟。过滤器将在一个会话（即真实过滤器会话（RFS））期间从主流烟雾中去除 NO，但不会在另一会话（即虚拟过滤器会话）期间去除 NO。 (DFS))。在每次吸烟之前和之后都会采集用于评估血浆尼古丁水平的血液样本，与 RFS 相比，DFS 中吸烟后血浆尼古丁水平显着高于吸烟前，这将支持我们的假设。我们将在每次吸烟期间获取烟瘾、负面影响和吸烟影响的测量结果，以比较两次吸烟期间吸烟的主观影响，将为后续研究评估提供基础。 NO 更充分地发挥作用这些研究的目的是为 FDA 提供数据，以决定是否以及如何监管香烟中的一氧化氮和/或其前体（例如硝酸盐），以通过减少吸烟的成瘾性来促进公众健康。