Abstract 046: Chronic Nicotine Inhalation Promotes the Development of Hypertension

Abstract

While smoking is a proven risk factor for stroke and heart attacks, whether it contributes to the development of hypertension is still unclear. Nicotine inhalation is thought to activate the sympathetic nervous system and could contribute to the development of dysautonomia and blood pressure (BP) dysregulation. The purpose of this study was to investigate a possible relationship between chronic nicotine inhalation and the development of hypertension. C57BL/6 mice (male, 8-12 weeks of age) were exposed to air or nicotine vapor (daily, 12 h on/off) for 8 weeks. BP was recorded weekly for 24 h (telemetry). Nicotine exposure was assessed by weekly measurement of serum cotinine levels, which showed an average of 599.0 ±54.3 ng/ml in nicotine-exposed mice. Nicotine exposure induced a time-dependent increase in systolic BP. Notably, 24-h BP recordings showed that by the end of the 7 th week, systolic BP of nicotine-exposed mice was more often in the hypertensive zone (as defined by the area under the curve [AUC] above the 130 mmHg threshold within a 24-h recording) compared to their air-exposed counterparts (AUC: 555 ±299 vs. 112 ±30, P=0.012 , n=12). This hypertensive response was validated in angiotensin-II (Ang-II)-infused mice (450 ng/kg/min, s.c., AUC: 1358 ±939 vs. 112 ±30, P<0.001 , n=5). At the end of nicotine exposure, urinary norepinephrine (NE) showed significant increase in both nicotine (108.9 ±9.8 vs. 79.53 ±5.7 ng/1ng creatinine, P=0.018 , n=9) and Ang-II groups (114.0 ±14 vs. 79.53 ±5.7 ng/1ng creatinine, P=0.016 , n=9), suggesting increased sympathetic activity in those mice. In addition, mice with global deletion of angiotensin converting enzyme type 2 (ACE2) showed a dramatic elevation in urinary NE level after nicotine exposure (157.8 ±8.5 vs. 79.53 ±5.7 ng/1ng creatinine, P<0.001 , n=9). These data suggest that ACE2 might be protective against nicotine inhalation-mediated rise in sympathetic activity. In summary, chronic nicotine inhalation promotes the development of hypertension, and this could be mediated through the elevated activity of sympathetic nervous system. Experiments are ongoing to confirm sympatho-excitation and a possible involvement of the renin-angiotensin system in chronic nicotine inhalation-induced hypertension.