Cardiovascular Effects Of Nicotine Research Articles

Acute Cardiovascular Effects of Vaping Compared to Cigarette Smoking in Young Adults

Background: First introduced as the safer alternative to smoking, vaping has become a popular activity among young adults. However, little is known about the potential health effects of vaping. This pilot project examined the acute cardiovascular effects of nicotine vapes/e-cigarettes (EC) in comparison to tobacco cigarettes (TC) in young adults in order to determine if vaping is more detrimental to cardiovascular health than traditional cigarettes.
 Methods: 16 healthy participants (7 M, 9 F; 20.2 ± 1.9 years) were recruited to participate in the study. Anthropometric measures were determined upon entry into the study. Circulatory measures (heart rate [HR], blood pressure [BP] and heart rate variability [HRV]) were measured prior to and 10-min following vaping or cigarette smoking and in response to an orthostatic challenge.
 Results: Resting circulatory and HRV measures were not different between chronic EC-users and TC-smokers. Vaping and cigarette smoking induced a significant increase in cardiovascular measures (HR and BP) but not HRV measures. Both groups responded similarly to the orthostatic challenge prior to and following vaping/smoking.
 Conclusion: These results indicate that, from a cardiovascular perspective, vaping induces similar acute effects as cigarette smoking and that young adults should be counselled about these adverse effects accordingly.

Long-term cardiovascular reprogramming by short-term perinatal exposure to nicotine's main metabolite cotinine.

Gather 'proof-of-concept' evidence of the adverse developmental potential of cotinine (a seemingly benign biomarker of recent nicotine/tobacco smoke exposure). Pregnant C57 mice drank nicotine- or cotinine-laced water for 6 wks from conception (NPRE = 2% saccharin + 100 μg nicotine/mL; CPRE = 2% saccharin + 10 μg cotinine/mL) or 3 wks after birth (CPOST = 2% saccharin + 30 μg cotinine/mL). Controls drank 2% saccharin (CTRL). At 17 ± 1 weeks (male pups; CTRL n = 6; CPOST n = 6; CPRE n = 8; NPRE n = 9), we assessed (i) cardiovascular control during sleep; (ii) arterial reactivity ex vivo; and (iii) expression of genes involved in arterial constriction/dilation. Blood cotinine levels recapitulated those of passive smoker mothers' infants. Pups exposed to cotinine exhibited (i) mild bradycardia - hypotension at rest (p < 0.001); (ii) attenuated (CPRE , p < 0.0001) or reverse (CPOST ; p < 0.0001) BP stress reactivity; (iii) adrenergic hypocontractility (p < 0.0003), low protein kinase C (p < 0.001) and elevated adrenergic receptor mRNA (p < 0.05; all drug-treated arteries); and (iv) endothelial dysfunction (NPRE only). Cotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion into cotinine. Low-level exposure to this metabolite may pose unrecognised perinatal risks. Adults must avoid inadvertently exposing a foetus or infant to cotinine as well as nicotine.

Genetic and Pharmacokinetic Determinants of Response to Transdermal Nicotine in White, Black, and Asian Nonsmokers

The aim of the study was to examine genetic, pharmacokinetic and demographic factors that influence sensitivity to nicotine in never smokers. Sixty never smokers, balanced for gender and race (Caucasian, Blacks and Asian), wore 7 mg nicotine skin patches for up to 8 hours. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in 9 subjects and was strongly associated with rate of rise and peak concentrations of plasma nicotine. Toxicity, subjective and cardiovascular effects of nicotine were associated with the presence of reduced function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when the latter are used for treating medical conditions in non-smokers, and possibly in vulnerability to developing nicotine dependence.

Patterns of nicotinic receptor antagonism II: Cardiovascular effects in rats

BackgroundTobacco cessation pharmacotherapies currently are limited to nicotine itself, the partial nicotine agonists varenicline and cytisine, and the antidepressant bupropion. Compared with agonists, nicotinic antagonists such as the noncompetitive, nonselective compound mecamylamine, and the competitive, α4β2-preferring antagonist dihydro-β-erythroidine (DHβE) may be a novel approach to the treatment of tobacco smoking as both are effective antagonists of nicotine's central effects. Considering nicotinic acetylcholine receptors mediate critical peripheral effects of acetylcholine, such as cardiovascular effects, it is important to study how nicotinic antagonists would alter the cardiovascular system and the cardiovascular changes induced by nicotine. MethodsThe effects of several nicotinic agonists and antagonists on blood pressure and heart rate were measured in conscious, unrestrained rats following parenteral administration using a telemetry system. ResultsNicotine and other nicotinic receptor agonists (epibatidine, varenicline, and cytisine) produced similar increases in blood pressure, whereas their effects on heart rate were biphasic. The cardiovascular changes were attenuated by the nonselective nicotine antagonist, mecamylamine, but the peripherally restricted antagonist hexamethonium blocked only the agonist-induced changes in blood pressure. The α7-preferring antagonist, MLA, and the α4β2-preferring antagonist, DHβE, were much less effective in blocking the agonist-induced cardiovascular changes, indicating that nicotine's cardiovascular effects, are due to activation at autonomic ganglia involving nicotinic receptor subtypes other than α4, α7, or β2. ConclusionsThe data indicate that the cardiovascular effects of nicotine and nicotine-like agents are mediated through receptor mechanisms that are distinct from those that mediate the central effects of nicotine.

Transdermal Nicotine Replacement Therapy Safety in Patients with Cardiovascular Disease

Purpose The safety and efficacy of nicotine replacement therapy in patients with stable cardiovascular disease and following an acute coronary event are reviewed. Summary Physicians have been hesitant to prescribe nicotine replacement therapy (NRT) in patients with cardiac disease due to the reported harmful cardiovascular effects of nicotine, including an increase in heart rate and blood pressure, as well as its possible contribution to the pathogenesis of coronary artery disease and sudden cardiac death. However, several studies have shown that NRT is safe following myocardial infarction and is preferred over continued cigarette smoking. One cohort study assessed the safety and efficacy of transdermal NRT in smokers admitted for acute coronary syndromes and found no difference in mortality versus patients given a placebo. Additionally, the cost of NRT should not be viewed as a barrier due to the long-term savings in preventable hospitalizations following additional cardiovascular events. Conclusion Transdermal NRT was found to be safe and effective in patients with acute myocardial infarction and with a known history of cardiovascular disease. It has also proven to be effective in smoking cessation, which eliminates the most important risk factor for an acute coronary event. NRT showed no increased frequency in mortality or other cardiac adverse events.

Critical Role of Peripheral Actions of Intravenous Nicotine in Mediating Its Central Effects

In addition to its direct action on central neurons, nicotine (NIC) activates multiple nicotinic acetylcholine receptors localized on afferent terminals of sensory nerves at the sites of its administration. Although the activation of these receptors is important in mediating the primary sensory and cardiovascular effects of NIC, their role in triggering and maintaining the neural effects of NIC remains unclear. Using high-speed electroencephalography (EEG) and electromyography (EMG) recordings in freely moving rats, we showed that NIC at low intravenous (i.v.) doses (10-30 μg/kg) induced rapid, strong, and prolonged EEG desynchronization both in the cortex and ventral tegmental area (with decreases in α and robust increases in β and γ frequencies) and neck EMG activation that began during the injection (∼5 s). EEG and EMG effects of NIC were drastically reduced by pre-treatment with hexamethonium, a peripherally acting NIC antagonist, and the immediate EEG effects of NIC were strongly inhibited during urethane anesthesia. Although NIC pyrrolidine methiodide, a quaternary NIC analog that cannot enter the brain, also induced rapid EEG desynchronization, its effects were much shorter and weaker than those of NIC. Therefore, NIC by acting on peripheral nicotinic receptors provides a major contribution to its rapid, excitatory effects following i.v. administration. Since this action creates a sensory signal that rapidly reaches the brain via neural pathways and precedes the slower and more prolonged direct actions of NIC on brain cells, it could have a major role in associative learning and changes in the behavioral and physiological effects of NIC following its repeated use.

Influence of menstrual cycle on cytochrome P450 2A6 activity and cardiovascular effects of nicotine*

The phase of the menstrual cycle has been reported to affect frequency of smoking, withdrawal symptoms, and the likelihood of smoking cessation in women. Cytochrome P450 (CYP) 2A6 is primarily responsible for the metabolism of nicotine. Our objective was to evaluate the effect of the phase of the menstrual cycle on the activity of CYP2A6 and the cardiovascular effects of nicotine. Eleven healthy, nonsmoking women received a 30-minute combined infusion of deuterium-labeled nicotine and cotinine (0.5 microg . kg(-1) . min(-1) of each compound) during the midfollicular and midluteal phases of the menstrual cycle. Nicotine and cotinine pharmacokinetic parameters and plasma adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine responses were measured over time. There were no biologically or statistically significant differences in the comparison of menstrual cycle phases with regard to the pharmacokinetics of nicotine and cotinine. Nicotine clearance was 1000 +/- 315 mL/min and 1047 +/- 271 mL/min in the follicular and luteal phases, respectively (geometric mean ratio, 1.06; 90% confidence interval, 0.87-1.29). Cotinine clearance was 44 +/- 20 mL/min and 55 +/- 42 mL/min in the follicular and luteal phases, respectively (geometric mean ratio, 1.13; 90% confidence interval, 0.90-1.41). Nicotine infusion increased blood pressure, heart rate, and epinephrine concentrations. There were no differences in catecholamine, ACTH, or hemodynamic responses to nicotine infusion between menstrual cycle phases, although norepinephrine concentrations were constantly higher in the luteal phase compared with the follicular phase. CYP2A6 activity is not affected by menstrual cycle phase, and it is unlikely that menstrual cycle-related smoking habits of women are determined by changes in nicotine pharmacokinetics. The effects of nicotine on plasma ACTH and catecholamine levels and hemodynamic parameters are not altered by menstrual cycle phase in healthy, nonsmoking women.

Cardiovascular effects of nicotine, chlorisondamine, and mecamylamine in the pigeon.

Chlorisondamine and mecamylamine are nicotinic antagonists that produce both ganglionic and central blockade. Chlorisondamine, when administered as a large systemic dose, produces a persistent central block, despite being charged. The present study evaluated the cardiovascular effects of chlorisondamine. Shortly after administration, chlorisondamine (0.10, 1, and 10 mg/kg i.m.) lowered blood pressure significantly and decreased heart rate at the low dose (0.1 mg/kg i.m.) and increased heart rate at the high dose (10 mg/kg i.m.). Mecamylamine (1 and 10 mg/kg i.m.) also lowered blood pressure and heart rate. After both antagonists, heart rate returned to baseline values within 90 min and blood pressure within 24 h. Low doses of nicotine (0.01-0.03 mg/kg i.m.) lowered blood pressure but did not affect heart rate. Higher doses (0.10-3.2 mg/kg i.m.) transiently increased blood pressure and heart rate. Subsequent to antagonist administration, nicotine was administered to determine whether either drug blocked the cardiovascular effects of nicotine. Chlorisondamine (0.1, 1, and 10 mg/kg i.m.) administered 30 min before nicotine blocked the increases in blood pressure and heart rate. Only the high dose (10 mg/kg i.m.) of chlorisondamine administered 24 h before nicotine produced a blockade of nicotine's pressor effect. This block diminished within 3 days. Mecamylamine (1 mg/kg i.m.) antagonized only nicotine's tachycardic effect. Longer pretreatment with mecamylamine (10 mg/kg, 24 h before nicotine challenge) did not antagonize the cardiovascular effects of nicotine. Thus, chlorisondamine produces a longer lasting blockade of nicotine's cardiovascular effects than mecamylamine.

Pharmacokinetic disposition of multiple-dose transdermal nicotine in healthy adult smokers.

The pharmacokinetics and cardiovascular effects of nicotine and its major metabolite, cotinine, were characterized during repeated once-daily application for 5 days of a 30-cm2 nicotine transdermal system, Nicotine TTS (Habitrol), to nine healthy, black, adult, male smokers. Subjects abstained from smoking throughout the study. Pharmacokinetic analysis indicated that nicotine was delivered from Nicotine TTS for the 24-hr application period averaging 0.76 mg/cm2/24 hr, and at a relatively constant rate compared to other modes of drug administration. The transdermal clearance of nicotine, 1351 ml/min, coincided with reported values following intravenous nicotine administration; however, the terminal-phase half-life, 5.0 hr, did not. An analysis of the components of variance contributing to the variability in nicotine delivery from repetitive application of Nicotine TTS indicated that the in vivo transdermal permeation of nicotine is rate limited by both the device and the intrinsic skin conductivity. Clinical cardiovascular side effects were negligible as an apparent result of subclinical vasopressive nicotine concentrations, although drug activity with regard to other effects was manifested.

Acute tolerance to the cardiovascular effects of nicotine

Acute tolerance to cardiovascular effects of nicotine was examined by presenting to male smokers a single administration of each of three different doses of nicotine (0.5, 1.0, 2.0 mg) or a placebo (0 mg) in a brief series of nasal spray boluses to mimic nicotine intake via smoking. Each dose was presented on a separate occasion. Changes in heart rate, systolic and diastolic blood pressure, finger pulse amplitude (peripheral vasoconstriction) and, in a subsample, plasma nicotine concentration were assessed during and after dose administration. Acute tolerance to nicotine was determined by comparing responses at ascending plasma nicotine concentrations during dose administration with the responses at comparable descending plasma concentrations following administration. For each nicotine dose, there was substantial acute tolerance to blood pressure, but less tolerance to heart rate (except for 0.5 mg), and little tolerance to pulse amplitude responses. These findings indicate that cardiovascular adaptation to nicotine during cigarette smoking may be rapid but variable in magnitude depending on the response being measured.

Cardiovascular responses to intracisternal administration of nicotine in rats.

The administration of nicotine into the cisterna magna evoked a delayed depressor effect with an initial pressor effect in anaesthetized rats. The depressor response was accompanied by a bradycardia. The cardiovascular effects of nicotine were abolished after intracisternal administration of hexamethonium but not after atropine given via the same route. Intravenous administration of methylatropine abolished the bradycardic response to nicotine but did not affect the blood pressure responses. The pressor effect of nicotine was abolished by intravenous administration of phenoxybenzamine. The cardiovascular effects of nicotine injected intracisternally were abolished when the diffusion of nicotine onto an area around the area postrema was interrupted using a polyethylene tube. In contrast, nicotine applied to the area produced a marked pressor--depressor response. It is concluded that the cardiovascular responses to intracisternal administration of nicotine result from the activation of central nicotinic receptor sites that may be present around the area postrema.

Cardiovascular effects of nicotine in the conscious dog: Modification by changes in autonomic tone

Studies were performed in conscious dogs in which catheters had previously been positioned for long-term use in the right atrium, right ventricle, pulmonary artery and central aorta. Doses of less than 200 μ g of nicotine injected into the right atrium produced no significant hemodynamic effects. A dose of 200 μ g of nicotine produced initial tachycardia, a subsequent hypertensive response and reflex bradycardia. A 400 μ g dose of nicotine produced a triphasic response: (1) a 2 to 4 second sinus arrest, (2) subsequent sinus tachycardia and marked hypertensive response, and (3) reflex bradycardia with persistent increases in right ventricular end-diastolic pressure. Arterial administration of nicotine in similar doses produced only hypertension and reflex bradycardia. No asystole or tachycardia was observed. Pretreatment with atropine eliminated the asystole produced by intravenous administration of nicotine but did not alter the reflex tachycardia occurring after intravenous or intraarterial administration of nicotine. Pretreatment with propranolol did not prolong the asystole occurring after intravenous administration of nicotine and did not diminish the peak increase in heart rate during phase 2. However, the reflex bradycardia was more pronounced after nicotine was given either intravenously or intraarterially. We conclude that, in the conscious dog, nicotine (1) releases acetylcholine in the right atrium, (2) may depress myocardial function, and (3) produces significant hypertension and reflex bradycardia.

Cardiovascular Effects of Nicotine and of Smoking

Cardiovascular Effects of Nicotine and of Smoking