Association of Chronic Nicotine Inhalation with Hypertension in Mice

Abstract

For decades it has been known that chronic tobacco smoke exposure is a risk factor for hypertension, predisposing to cardiovascular pathologies including stroke and heart failure. However, no prior study has evaluated the role of inhaled nicotine per se. Previous investigations found that subcutaneously‐administered nicotine acutely increases expression of angiotensin‐converting enzyme (ACE) and the angiotensin receptor (AT1R). These findings suggest RAS dysfunction may mediate nicotine‐induced hypertension through either increased expression of pro‐hypertensive proteins (ACE/AT1R) or suppressed expression of compensatory agents (ACE2/MasR).Accordingly, we hypothesized that chronic nicotine inhalation promotes hypertension by inducing RAS dysfunction within autonomic brain nuclei. To test this hypothesis we exposed male (n = 64) and female (n = 44) mice to air (control) or twelve hours of nicotine vapor nightly for eight weeks. Mean nocturnal systolic blood pressure (telemetry) increased between the baseline and final week of nicotine exposure (males: +19.71 ±0.65 mmHg, F = 528.2, n = 5, p < 0.0001; females: +14.04 ±0.85 mmHg, F = 322.7, n = 4, p < 0.0001). In females, a trend towards elevated urinary norepinephrine was observed (t = 1.751, p = 0.0993). In a pilot study, when we exposed rats for 3 weeks to 14 hours of nicotine nightly, the hypothalamic ACE2 mRNA levels were reduced (t = 2.490, p < 0.05). In mice we found a trend towards increased expression of MasR mRNA in this brain region (t = 2.373, p = 0.0766).Together, these findings suggest that nicotine inhalation contributes to high blood pressure, possibly through enhanced sympathetic activity. Mechanistically, our pilot data indicate that impaired ACE2 expression occurs in tandem with a compensatory increase in MasR in the hypothalamus of subjects inhaling nicotine. Future studies will elucidate activity of additional RAS contributors in cell culture and clarify the nature of autonomic dysfunction in vivo (e.g., increased sympathetic output vs decreased vagal tone). Collectively, this project will provide crucial information regarding the risk of hypertension in users of nicotine inhalation devices (i.e. e‐cigarettes), improving the ability of clinicians to treat this condition.Support or Funding InformationThis work was supported by NIH NHLBI grants 1R01 HL135635 and 2R01 HL093178.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.