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Effects of Chronic Nicotine Inhalation on Systemic and Pulmonary Blood Pressure and Right Ventricular Remodeling in Mice
Hypertension ( IF 8.3 ) Pub Date : 2020-05-01 , DOI: 10.1161/hypertensionaha.119.14608
Joshua M Oakes 1 , Jiaxi Xu 2, 3 , Tamara M Morris 2, 3 , Nicholas D Fried 1 , Charlotte S Pearson 1 , Thomas D Lobell 1, 3 , Nicholas W Gilpin 1, 3 , Eric Lazartigues 2, 3, 4 , Jason D Gardner 1, 4 , Xinping Yue 1
Affiliation  

Supplemental Digital Content is available in the text. Cigarette smoking is the single most important risk factor for the development of cardiovascular and pulmonary diseases; however, the role of nicotine in the pathogenesis of these diseases is incompletely understood. The purpose of this study was to examine the effects of chronic nicotine inhalation on the development of cardiovascular and pulmonary disease with a focus on blood pressure and cardiac remodeling. Male C57BL6/J mice were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Systemic blood pressure was recorded weekly by radio-telemetry, and cardiac remodeling was monitored by echocardiography. At the end of the 8 weeks, mice were subjected to right heart catheterization to measure right ventricular systolic pressure. Nicotine-exposed mice exhibited elevated systemic blood pressure from weeks 1 to 3, which then returned to baseline from weeks 4 to 8, indicating development of tolerance to nicotine. At 8 weeks, significantly increased right ventricular systolic pressure was detected in nicotine-exposed mice compared with the air controls. Echocardiography showed that 8-week nicotine inhalation resulted in right ventricular (RV) hypertrophy with increased RV free wall thickness and a trend of increase in RV internal diameter. In contrast, there were no significant structural or functional changes in the left ventricle following nicotine exposure. Mechanistically, we observed increased expression of angiotensin-converting enzyme and enhanced activation of mitogen-activated protein kinase pathways in the RV but not in the left ventricle. We conclude that chronic nicotine inhalation alters both systemic and pulmonary blood pressure with the latter accompanied by RV remodeling, possibly leading to progressive and persistent pulmonary hypertension.

中文翻译:

慢性尼古丁吸入对小鼠全身血压和肺血压以及右心室重构的影响

文本中提供了补充数字内容。吸烟是心血管和肺部疾病发展的最重要的危险因素;然而,尼古丁在这些疾病发病机制中的作用尚不完全清楚。本研究的目的是检查慢性尼古丁吸入对心血管和肺部疾病发展的影响,重点是血压和心脏重塑。雄性 C57BL6/J 小鼠暴露于空气(对照)或尼古丁蒸气(每天,12 小时开/12 小时关)8 周。每周通过无线电遥测记录全身血压,并通过超声心动图监测心脏重塑。在 8 周结束时,对小鼠进行右心导管插入术以测量右心室收缩压。暴露于尼古丁的小鼠在第 1 周至第 3 周表现出全身血压升高,然后在第 4 周至第 8 周恢复到基线,表明对尼古丁产生耐受性。在 8 周时,与空气对照组相比,在暴露于尼古丁的小鼠中检测到右心室收缩压显着增加。超声心动图显示 8 周尼古丁吸入导致右心室 (RV) 肥大,右心室游离壁厚度增加,右心室内径有增加的趋势。相反,尼古丁暴露后左心室没有明显的结构或功能变化。从机制上讲,我们观察到 RV 中血管紧张素转换酶的表达增加和促分裂原活化蛋白激酶途径的激活增强,但在左心室中没有。
更新日期:2020-05-01
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