Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary health impacts of these nicotine-containing devices. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in mice. These changes were associated with upregulated RV angiotensin-converting enzyme (ACE). Angiotensin-II receptor blockers (ARBs) have been shown to reverse cigarette smoking-induced PH in rats. ACE inhibitor and ARB use in a large retrospective PH patient cohort is associated with improved survival. Here, we utilized losartan (an ARB specific for angiotensin-II type 1 receptor) to further explore nicotine-induced PH. Male C57BL/6 mice received nicotine vapor for 12 hours per day, and exposure was assessed using serum cotinine to achieve levels comparable to human smokers or electronic cigarette users. Mice were exposed to nicotine for 8 weeks and a subset was treated with losartan via osmotic minipump. Cardiac function was assessed using echocardiography and catheterization. Although nicotine exposure increased angiotensin-II in the RV and lung, this finding was non-significant. Chronic, inhaled nicotine significantly increased RV systolic pressure and RV free wall thickness versus air control. These parameters were significantly lower in mice receiving both nicotine and losartan. Nicotine significantly increased RV internal diameter, with no differences seen between the nicotine and nicotine-losartan group. Neither nicotine nor losartan effect left ventricular structure or function. These findings provide the first evidence that antagonism of the angiotensin-II type 1 receptor can ameliorate chronic, inhaled nicotine-induced PH and RV remodeling.

中文翻译：

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血管紧张素-II 1 型受体介导吸入尼古丁诱导的肺动脉高压和右心室重构。


青少年和年轻人中电子烟的使用正在迅速增加，但人们对这些含尼古丁装置对心肺健康的长期影响知之甚少。我们的研究小组之前已经证明，长期吸入尼古丁会诱发小鼠肺动脉高压（PH）和右心室（RV）重塑。这些变化与 RV 血管紧张素转换酶 (ACE) 上调有关。血管紧张素 II 受体阻滞剂 (ARB) 已被证明可以逆转吸烟引起的大鼠 PH。在大型回顾性 PH 患者队列中使用 ACE 抑制剂和 ARB 与提高生存率相关。在这里，我们利用氯沙坦（一种针对血管紧张素-II 1 型受体特异性的 ARB）来进一步探索尼古丁诱导的 PH。雄性 C57BL/6 小鼠每天接受尼古丁蒸气 12 小时，并使用血清可替宁评估暴露程度，以达到与人类吸烟者或电子烟使用者相当的水平。小鼠接触尼古丁 8 周，其中一部分小鼠通过微型渗透泵接受氯沙坦治疗。使用超声心动图和导管插入术评估心脏功能。尽管接触尼古丁会增加右心室和肺部的血管紧张素-II，但这一发现并不显着。与空气对照相比，长期吸入尼古丁显着增加了右心室收缩压和右心室游离壁厚度。在接受尼古丁和氯沙坦治疗的小鼠中，这些参数显着降低。尼古丁显着增加了 RV 内径，尼古丁组和尼古丁-氯沙坦组之间没有观察到差异。尼古丁和氯沙坦都不影响左心室结构或功能。 这些发现提供了第一个证据，证明血管紧张素-II 1 型受体的拮抗作用可以改善慢性、吸入尼古丁诱导的 PH 和 RV 重塑。