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。

电子烟的使用在青年和年轻人中迅速增加，但对于这些含尼古丁装置的长期心肺健康影响知之甚少。我们小组先前已经证明，慢性吸入尼古丁可诱导小鼠肺动脉高压 (PH) 和右心室 (RV) 重塑。这些变化与上调的 RV 血管紧张素转换酶 (ACE) 有关。血管紧张素-II 受体阻滞剂 (ARB) 已被证明可以逆转吸烟诱导的大鼠 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（一种血管紧张素-II 1 型受体特异性 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汽 12 小时，并使用血清可替宁评估暴露，以达到与人类吸烟者或电子烟使用者相当的水平。将小鼠暴露于尼古丁 8 周，并通过渗透微型泵用氯沙坦处理一个子集。使用超声心动图和导管插入术评估心脏功能。尽管尼古丁暴露增加了 RV 和肺中的血管紧张素-II，但这一发现并不显着。与空气控制相比，慢性吸入尼古丁显着增加 RV 收缩压和 RV 游离壁厚度。在接受尼古丁和氯沙坦的小鼠中，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-氯沙坦组之间没有差异。尼古丁和氯沙坦都不影响左心室结构或功能。