Acute effects of electronic cigarettes on arterial pressure and peripheral sympathetic activity in young non-smokers

E-cigarettes like the JUUL are marketed as an alternative to smoking for those who want to decrease the health risks of tobacco. Tobacco cigarettes increase heart rate (HR) and arterial pressure (AP), while reducing muscle sympathetic nerve activity (MSNA) through sympathetic baroreflex inhibition. The acute effects of e-cigarettes on AP and MSNA have not been reported: our purpose was to clarify this issue. Using a randomized crossover design, participants inhaled on a JUUL containing nicotine (59 mg/ml) and a similar placebo e-cigarette (0 mg/ml). Experiments were separated by ~1 month. We recorded baseline ECG, AP (n=15), and MSNA (n=10). Subjects rested for 10 min, (BASE) and then inhaled once every 30 s on an e-cigarette that contained nicotine or placebo (VAPE) for 10 min followed by a 10-min recovery (REC). Data were expressed as Δmeans±SE from BASE. HR increased in the nicotine condition during VAPE and returned to BASE values in REC (5.0±1.3 nicotine vs 0.1±0.8 b/min placebo, during VAPE P<.01). AP increased in the nicotine condition during VAPE and remained elevated during REC. (6.5±1.6 nicotine vs 2.6±1 mmHg placebo, during VAPE and 4.6.0±1.7 nicotine vs 1.4±1.4 mmHg placebo during REC; p<.05). MSNA decreased from BASE to VAPE and did not restore during REC (-7.1±1.6 nicotine vs 2.6±2 bursts/min placebo during VAPE and -5.8±1.7 nicotine vs 0.5±1.4 placebo during REC; p<.05). Our results show that acute e-cigarette usage increases mean arterial pressure leading to a baroreflex mediated inhibition of MSNA.

Abstract 2403: Inspiratory Muscle Training Decreases Central and Peripheral Sympathetic Activity Improves Reflex Vasodilatory Blood Flow in Patients with Chronic Heart Failure

Background: Inspiratory muscle training (IMT) improves functional capacity of patients with CHF but the mechanisms of this effect are unknown. Objective: We tested the hypothesis that IMT could decrease sympathetic activity and improve the reflex muscle vasodilatory response during exercise in patients (CHF) and inspiratory muscle weakness. Methods: Six patients with CHF and inspiratory muscle weakness (maximal inspiratory pressure <70% of predicted) NYHA Class II–III, EF <35%, peak VO(2) < 20 ml/kg/min, were submitted to a IMT during 12 weeks (30 minute breathing with an inspiratory resistance of 30% of maximal inspiratory pressure). Muscle sympathetic nerve activity (MSNA) was recorded by microneurography, LF (sympathetic) and HF (parasympathetic) components of the heart rate variability and LF/HF ratio were assessed by the use of power spectral analysis of RR interval. Forearm blood flow (FBF) was measured by venous occlusion plethysmography at baseline and during hand grip (HG) manouver. Paired student t-test was used to analyze the impact of IMT in this population. Results: Compared to baseline, IMT significantly (p < 0,05) caused: an increase in inspiratory muscle force by 130%; a 15% reduction in MSNA (40 ± 1 vs 33 ± 1 bursts/min); an increase in forearm blood flow (0.8+/−0.1 mL/min/100 g) during HG manouver; a decrease in LF% (59 ± 5 vs 39 ± 3 U); an increase in HF% (40 ± 5 vs 61 ± 3 U); a decrease in LF/HF ratio (1,74 vs 0,66). Conclusions: Twelve weeks of Inspiratory muscle training in patients with CHF and inspiratory muscle weakness promoted a significant improvement in cardiovascular parameters, such as increase in limb blood flow, cardiac autonomic balance and baroreflex sensitivity, associated with a decrease in peripheral sympathetic activity.

Interleukin-6 (IL-6) is secreted from the brain after intracerebroventricular injection of IL-1 beta in rats

To test the hypothesis that the brain is a source of the interleukin-6 (IL-6) that appears in the peripheral circulation of rats after intracerebroventricular (icv) injection of IL-1 beta, the concentration of bioactive IL-6 in superior sagittal sinus (SSS) blood plasma was compared with aortic plasma 4 h after icv injection of 100 ng of recombinant human IL-1 beta at a time at which cerebrospinal fluid (CSF) IL-6 concentration was found to be markedly elevated. In three separate experiments, CSF IL-6 concentration (pg/ml; values are means +/- SE) was significantly elevated after icv IL-1 beta compared with saline control injections (25,879 +/- 11,472 vs. 35.5 +/- 5; 32,323 +/- 4,945 vs. 128 +/- 29; 114,410 +/- 33,563 vs. 848 +/- 250, respectively). The concentration of plasma IL-6 (pg/ml) in the aortas of rats injected intracerebroventricularly with IL-1 was greater than in controls [252 +/- 93 vs. 36.7 +/- 8.3, P = 0.0037; 361 +/- 95 vs. 57 +/- 13, P = 0.02; 2,254 +/- 550 vs. 1,239 +/- 666, P = 0.26 (NS)]. In IL-1-injected animals, SSS venous plasma IL-6 (pg/ml) was greater than in the aorta in all three studies (1,617 +/- 357 vs. 252 +/- 93, P = 0.0011; 3,754 +/- 1,188 vs. 361 +/- 95, P = 0.024; 8,208 +/- 1,388 vs. 2,254 +/- 550, P = 0.0054). The concentration difference (pg/ml) between SSS and aorta was significantly greater after IL-1 beta injection than in diluent-injected animals (1,365 +/- 369 vs. 48.3 +/- 13, P = 0.0083; 3,393 +/- 1,203 vs. 126 +/- 59, P = 0.035; 5,954 +/- 1,260 vs. 494 +/- 774, P = 0.0042). Suppression of peripheral sympathetic activation by preganglionic cholinergic blockade (chlorisondamine, 250 micrograms sc) did not prevent the usual IL-1-induced elevation in aortic blood IL-6 (3,272 +/- 1,174 vs. 244 +/- 74 pg/ml, P = 0.0012) nor the increased SSS-aortic gradient (2,541 +/- 1,134 vs. 165 +/- 48, P = 0.0142 by Mann-Whitney comparison). Injection of rat/human corticotropin-releasing hormone (CRH; 10.0 micrograms) icv did not change IL-6 concentration in CSF or in peripheral blood. These studies demonstrated that the brain and/or its supporting structures are activated by icv IL-1 beta to release IL-6 into the blood and that the effect is not dependent on peripheral sympathetic activity or central mobilization of CRH. Direct secretion of IL-6 and possibly of other cytokines from the brain is postulated to be a pathway of neuroimmunomodulation.