Chronic Nicotine Inhalation Promotes the Development of Pulmonary Hypertension

Pulmonary hypertension is a condition of increased blood pressure within the arteries of the lungs, leading to clinical symptoms including shortness of breath, syncope, tiredness, chest pain, swelling of the legs, and a fast heartbeat. The exact cause of pulmonary hypertension is often unknown, but the risk factors include a family history, prior blood clots in the lungs, HIV/AIDS, cocaine use, and smoking. Nicotine is the addictive component of tobacco products including conventional cigarette, cigar, and the increasingly popular electronic cigarette (e‐cigarette). The purpose of this study was to examine the effects of chronic nicotine inhalation in the development of pulmonary hypertension. C57BL/6 mice (male, 8–12 weeks of age) were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Nicotine exposure was assessed by weekly measurement of serum cotinine levels (a more stable metabolite of nicotine), which showed a weekly average of 599.0 ± 54.28 ng/ml (mean ± SEM) in nicotine exposed mice. As the positive control, a subset of air‐exposed control mice were subjected to Angiotensin‐II (Ang‐II) infusion through subcutaneous osmotic mini‐pumps (450 ng/kg/min) for the last 4 weeks. At the end of the 8 weeks, mice were subjected to right heart catheterization (Millar SPR‐1000 Mikro‐Tip mouse pressure catheter) to measure the right ventricular systolic pressure (RVSP) followed by tissue collection. Nicotine exposed mice exhibited significantly increased RVSP (39.57 ± 4.17 mmHg, n=7) compared to the air‐exposed controls (22.31 ± 1.70 mmHg, n=8, P < 0.01 by unpaired student t‐test). Interestingly, the increase in RVSP by nicotine was as potent as Ang‐II infusion (38.00 ± 2.18 mmHg, n=7, P < 0.001 vs . air controls). Furthermore, our discovery quantitative proteomic analysis identified atrial natriuretic peptide receptor 1 and periostin among the over‐expressed proteins in the lungs from nicotine exposed mice compared to the air controls, both of which have been shown to be involved in the regulation of pulmonary blood pressure. We conclude that chronic nicotine inhalation promotes the development of pulmonary hypertension. In addition, to the immediate relevance to public health, our data suggest that nicotine users, especially young adults with e‐cigarette use, are at elevated risk for the development of pulmonary hypertension. Ongoing experiments are focusing on the mechanisms of nicotine‐induced pulmonary hypertension, including nicotine‐induced pulmonary vascular remodeling. Support or Funding Information This work was supported by the National Heart, Lung, and Blood Institute R01 HL135635 and the National Institute of General Medical Sciences P30 GM106392. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .