Oral administration of nicotine and plasma levels of ACTH and cortisol in smokers and non-smokers

Plasma ACTH and cortisol levels after oral administration of nicotine (chewing gum containing nicotine 2 mg) in short and long time (10 and 45 min) were studied in smokers and non smokers. Non smokers after short time administration showed significant rise in ACTH and cortisol. No modifications were seen in the other groups of subjects. These data confirm that nicotine stimulates hypophysis-adrenal axis in non smokers and that this effect is connected with nicotine contents of cigarettes rather than other volatile substances.     

男性吸烟者体重对烟碱引起的生热作用和儿茶酚胺释放的影响

本研究的目的是在中年男子中观察禁食情况下吸烟后烟碱对安静时能量消失（resting energy expenditure,REE)和血浆儿茶酚胺浓度的影响,并且在正常体重（BMI≤25kg/m^2),和超重（BMI＞25kig/m^2)吸烟者之间比较吸烟引起的REE和血浆儿茶酚胺的急性反应是否有差别,对32名禁食的男性吸烟者用间接测热法分别在吸烟前和吸2支含0．16mg烟碱（低烟碱）或2支含1．74mg烟碱（高烟碱）香烟30min后测定REE,同时测定血浆中烟碱和去甲肾上腺素浓度,正常体重组在吸低烟碱烟后和超重组不认在吸低烟碱烟或高烟碱烟后,REE和血浆儿茶酚胺均无明显改变,而在正常体重组中,吸高烟碱烟后血浆去甲肾上腺素浓度升,时REE增加7．2％,如果将血浆烟碱水平作为一个共变量进行分析,则吸烟后血浆去甲肾上腺素浓度和REE的改变也不明显,表明吸烟后的生热效应是因血浆烟碱浓度升高而引起的,体重对烟碱的生热效应能发生影响,在超重的吸烟者中烟碱的生热效应减弱,由此推测,正常体重的吸烟者在戒烟后,由于不再有吸烟引起的耗能生热,可能导致体重增加。     

ACTH and cortisol after cigarette smoke exposure during the dexamethasone suppression test in smokers and non-smokers

In this research the effect of nicotine, (smoke of cigarette), was studied in smokers and non smokers during dexamethasone inhibitory test (1 mg h 23.00). ACTH and cortisol plasma levels, physiologically suppressed at 08.00, increased, after 30 min from smoking, only in group of non smokers. These data suggest that nicotine, in non smokers, could induce a maximum stimulus on diencephalic structures, so to overcome the inhibition of dexamethasone.     

Changes in the levels of ACTH and cortisol after passive exposure to cigarette smoke in smokers and non-smokers

Plasma ACTH and cortisol levels were studied in smokers and non smokers, (exposed or not to smoke of the environment), after passive exposure to cigarette smoking. Non smokers, usually not exposed to smoke, show a rise in both hormones, whereas smokers and non smokers commonly exposed to smoke don't show any change in ACTH and cortisol levels. These data suggest that nicotine acts as an acute stimulus on the hypophysis-adrenal axis even passively inhaled.     

Hormones, nicotine, and cocaine: Clinical studies

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (< 20 min), ratings of “high” and “rush” began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.     

Self-titration by cigarette smokers

An 11-week crossover study was carried out in which 12 subjects smoked high-nicotine (1·84 mg standard yield) and low-nicotine (0·6 mg) cigarettes after an initial period of smoking their usual brands with a medium-nicotine yield (mean 1·4 mg). Plasma and urine nicotine concentrations, carboxyhaemoglobin (COHb) concentration, puffing behaviour, 24-hour cigarette consumption, and butt nicotine content were measured. The changes in plasma nicotine and blood COHb concentrations showed that the smokers compensated for about two-thirds of the difference in standard yields when switched to either high- or low-nicotine cigarettes. Thus, compared with the medium-nicotine brand, the intake of nicotine and carbon monoxide was only about 10% higher when subjects smoked the high-nicotine cigarettes, which had a standard yield 30-40% higher than the medium brands; and only about 15% lower when they smoked the low-nicotine cigarettes, which had a standard yield about 50% lower than the medium brands. But nicotine content and urine nicotine concentrations followed a similar pattern. Changes in puffing behaviour and in 24-hour cigarette consumption were only slight.The results show clear evidence of both upward and downward self-titration of nicotine and carbon monoxide (and tar) intakes when smokers change to cigarettes with standard yields that differ over the range studied.     

Effect of cigar smoking on carboxyhaemoglobin and plasma nicotine concentrations in primary pipe and cigar smokers and ex-cigarette smokers

Five ex-cigarette smokers and five primary pipe and cigar smokers each smoked a large cigar. Carboxyhaemoglobin (COHb) and plasma nicotine levels were measured. In the ex-cigarette smokers mean COHb rose from 2·9% to 9·6% and plasma nicotine from 79·0 nmol/l to 281 nmol/l (12·8-45·6 ng/ml). This response was similar to that of cigarette smokers smoking cigarettes, which indicated that the subjects had inhaled and absorbed significant amounts of nicotine. In the primary pipe and cigar smokers the mean COHb rose from 0·8% to 1·0% and the plasma nicotine from 21 nmol/l to 32 nmol/l (3·4-5·2 ng/ml), indicating neither significant inhalation nor significant nicotine absorption.Since ex-cigarette smokers do not seem to lose their habit of inhaling when they change to cigars, measures aimed at persuading smokers to switch to cigars will have little effect on their health. Pipe and cigar smokers who have never smoked cigarettes do not inhale, which probably accounts for their reduced incidence of coronary heart disease and lung cancer. But they also appear not to absorb nicotine, which suggests that nicotine is absorbed largely from the lung and that the buccal mucosa is unimportant. It also raises the interesting question of why primary pipe and cigar smokers do smoke.     

'Normal' cigarette smoking increases free cortisol in habitual smokers.

In habitual smokers salivary cortisol responses to cigarette smoking were investigated. In the first study, 31 adults assigned to two experimental groups smoked either one or two cigarettes of their preferred brand. Mean salivary cortisol levels were significantly elevated after smoking of two cigarettes. In the second study, 10 smokers and 10 nonsmokers provided saliva samples at 20 min intervals over a 12-hr period. While environmental stimuli were paralleled in both groups overall cortisol output was significantly elevated in the smokers. These data suggest that 'normal' cigarette smoking can increase free cortisol levels.     

Should intake of carbon monoxide be used as a guide to intake of other smoke constituents?

The relation between blood carboxyhaemoglobin (COHb) and plasma nicotine concentrations was studied in a group of 12 smokers smoking cigarettes of three levels of standard delivery. While the intake of carbon monoxide from a single cigarette was unrelated to the intake of nicotine, presmoking "trough" concentrations of the two substances (reflecting longer-term exposure) were highly correlated. Various other measures of nicotine exposure were at best only moderately correlated with blood nicotine concentrations. Thus trough COHb concentrations might be used to provide a reliable indication of the exposure to nicotine of individual smokers smoking the same type of cigarette, and of the relative exposure to nicotine of populations smoking cigarettes of different standard deliveries.     

Cigarette smoking may reduce plasma leptin concentration via catecholamines

BACKGROUND: Leptin might influence body weight among smokers. DESIGN: (A) Screening of plasma leptin levels in 222 sedentary, smoking and non-smoking middle-aged men. (B) Double-blind, placebo-controlled smoking intervention on smokers (n=31). (C) Non-smokers (n=40) received chewing gum with nicotine (2mg nicotine, n=23) or without nicotine (n=19). (D) The effects of nicotine (0.05 and 0.5 microg/mL) were monitored on leptin secretion and mRNA levels in a human placental cell line (BeWo) expressing leptin, a murine adipocyte cell line (3T3-L1) and human adipose tissue explants. RESULTS: (A) Plasma leptin levels in smoking men (8.4+/-8.4 ng/mL, n=100) was lower as compared to non-smokers (10.3+/-7.3 ng/mL, n=122) (P<0.001), even when adjusted for differences in body mass index (BMI) (P<0.001). (B) A significant reduction (P=0.02) in plasma concentration of leptin was found already after smoking one cigarette. Concomitant with the 3-5 fold increase in plasma nicotine concentration after the first cigarette, we observed increased plasma adrenaline levels (P=0.005). (C) There was no effect of nicotine on plasma leptin levels in non-smokers receiving nicotine-containing chewing gum, and plasma concentrations of catecholamines were unaltered. (D) There was no effect of nicotine on leptin mRNA expression after incubation with cells or adipose tissue. CONCLUSION: Cigarette smoking reduced plasma leptin concentration in vivo, whereas nicotine had no direct effect on leptin expression in vitro. Nicotine might indirectly reduce leptin secretion via enhanced plasma catecholamine concentration.     

Relationship between cigarette yields,puffing patterns,and smoke intake: evidence for tar compensation?

The relationship between cigarette yields (of nicotine, tar, and carbon monoxide), puffing patterns, and smoke intake was studied by determining puffing patterns and measuring blood concentrations of nicotine and carboxy-haemoglobin (COHb) in a sample of 55 smokers smoking their usual brand of cigarette. Regression analyses showed that the total volume of smoke puffed from a cigarette was a more important determinant of peak blood nicotine concentration than the nicotine or tar yield of the cigarette, its length, or the reported number of cigarettes smoked on the test day. There was evidence of compensation for a lower tar yield over and above any compensation for nicotine. When nicotine yield was controlled for, smokers of lower-tar cigarettes not only puffed more smoke from their cigarettes than smokers of higher-tar cigarettes but they also had higher plasma nicotine concentrations, suggesting that they were compensating for the reduced delivery of tar by puffing and inhaling a greater volume of smoke. The results based on the COHb concentrations were consistent with this interpretation. If an adequate intake of tar proves to be one of the main motives for smoking, then developing a cigarette that is acceptable to smokers and also less harmful to their health will be much more difficult.     

Puffing Frequency and Nicotine Intake in Cigarette Smokers

The smoking behaviour of 36 subjects smoking cigarettes with different filter retention efficiencies for nicotine was studied. Subjects were observed while performing various tasks on a driving simulator and also during a resting period after the tasks. Smokers of cigarettes with high-retention filters took more frequent puffs and obtained nearly the same amount of nicotine as smokers of cigarettes with low-retention filters, both while performing the tasks and during the resting period. Smokers of both types of cigarettes took significantly more puffs and obtained more nicotine per unit time during the resting period than during the tasks. The results are compatible with the possibility that smokers automatically adjust the nicotine dose obtained from a cigarette to some “optimum” level which may vary with different activities.     

Influence of Smoking on Hormone Secretion in Obese and Lean Female Smokers

Smoking exerts influences on the secretion of several hormones which are abnormal in obesity. Previous studies have mainly been performed in non-obese men, and data from non-obese and obese women are scarce. The aim of the present study was therefore to identify the effect of smoking on hormone secretions in obese and lean female smokers. The study was performed in 10 obese and 8 lean, premenopausal, healthy smokers. All subjects were tested once under experimental and once under control conditions (not smoking) in randomized order. The women smoked two non-filtered cigarettes during 4 minutes each. Blood pressure and heart rate were measured 30 minutes before smoking, at the start of smoking (time 0) and then after 5, 10, 20, 30, 45 and 60 minutes. Blood samples were taken for determination of serum concentrations of adrenocorticotropic hormone (ACTH), Cortisol, prolactin (PRL), growth hormone (GH) and thyroid stimulating hormone (TSH) at the same time points except at 5 minutes. Heart rate rose in both groups during smoking. Systolic and diastolic blood pressure was increased only in the obese subjects. Cortisol and ACTH increased in both groups, while TSH, PRL and GH were unchanged in both groups. We conclude that lean and obese smoking women seem to respond rather similarly to smoking in the hemodynamic and endocrine variables measured in this report with the possible exception of blood pressure where the obese women tended to show more pronounced increases.     

Cortisol inhibits ACTH but not the AVP response to hypoxaemia in fetal lambs at days 123-128 of gestation

During acute hypoxemia in fetal sheep the elevation in ACTH concentration in the fetal circulation at days 125-129 is greater than that at term, but similar rises in AVP occur at both times. To examine whether the diminished ACTH response is due to elevated endogenous cortisol, and if there is differential control of ACTH and AVP release in hypoxemia, we infused either vehicle or cortisol (5 micrograms/min) into fetal sheep at days 123-128 for 5 h before and then during a 2-h period of acute hypoxemia (mean PaO2 decrease 8.2 mmHg) without acidemia. During cortisol infusion, plasma cortisol rose to 40-50 ng/ml, similar to values in term fetuses. In vehicle-infused fetuses, cortisol rose from 2.1 to 7.0 ng/ml at +1 to +2 h of hypoxemia. ACTH rose significantly during hypoxemia in the vehicle-infused fetuses, and this response was attenuated by cortisol infusion. In contrast, fetal AVP rose significantly during hypoxemia both in the presence and absence of cortisol infusion. Fetal breathing movements, and electroocular activity decreased during hypoxemia, and these responses were not altered by cortisol. We conclude that cortisol exerts differential negative feedback on ACTH but not on AVP release during hypoxemia. The maintained AVP response may facilitate cardiovascular adjustments of the fetus to hypoxemia even when endogenous cortisol is elevated, such as near term.     

Repeated stress alters the ability of nicotine to activate the hypothalamic-pituitary-adrenal axis

Acute nicotine administration has been shown to activate the hypothalamic-pituitary-adrenal (HPA) axis and stimulate secretion of adrenocorticotrophic hormone (ACTH), corticosterone/cortisol and beta-endorphin (beta-END) in both rodents and humans, raising the possibility that activation of the HPA axis by nicotine may mediate some of the effects of nicotine. Since stress can increase the risk of drug use and abuse, we hypothesized that repeated stress would increase the ability of nicotine to stimulate the secretion of HPA hormones. To test our hypothesis, mice were exposed to repeated stress (swimming in 15 degrees C water for 3 min/day for 5 days) and killed 15 min after injection of saline or nicotine (0.1 mg/kg, s.c.). Repeated exposure to stress increased the ability of nicotine to stimulate plasma ACTH (p<0.05) and beta-END (p<0.05), but not corticosterone secretion. In contrast, repeated exposure to stress increased the post-saline injection levels of corticosterone (p<0.05), but not ACTH and beta-END. The present results suggest that chronic stress leads to an enhanced sensitivity of some components of the HPA axis to a subsequent nicotine challenge.     

Why smoke fewer cigarettes?

Sixteen volunteers were tested when smoking their own brand of cigarettes normally and when smoking half their usual number of cigarettes. While smoking half their usual amount the subjects changed their inhalation behaviour. Over this period the percentages of carboxyhaemoglobin were not significantly different from steady-state values where plasma nicotine concentration rose significantly. With the reduction in cigarettes there were significant falls in haemoglobin concentration, packed cell volume, and red cell count. These findings suggest that the advice given to patients to smoke fewer cigarettes should be accompanied by a warning against increasing inhalation. Patients who say that they have reduced their smoking but who have unaltered carboxyhaemoglobin concentrations should not be discredited.     

Differences in cortisol, aldosterone and testosterone responses to ACTH 1-17 administered at two different times of day

The effects of 100 micrograms, i.m. of the analog ACTH 1-17 administered at 0800 and 1800 on the secretion of cortisol, aldosterone and testosterone have been studied in normal subjects: 8 male and 8 female. The group as a whole and the males had significantly greater absolute and percent increments in plasma cortisol after administration at 1800. In the females, there was only a greater percent increment in cortisol after the evening administration. The heptadecapeptide always significantly stimulated serum aldosterone, with no difference between the two times of administration. In the females, ACTH 1-17 significantly stimulated testosterone, with a more protracted secretion after the evening administration. In the males, there was always a significant testosterone decrease after the administration of the drug, with no difference between morning and evening. In conclusion, 100 micrograms i.m. of the analog ACTH 1-17 stimulates cortisol secretion more when given during the circadian nadir of plasma cortisol, but only in men. ACTH 1-17 increases testosterone in women and decreases it in men, whereas it seems to increase aldosterone secretion in both sexes.     

Studies on the release of dopamine-beta-hydroxylase by nicotine (author's transl)

Comparative studies were made on the release of DBH by adrenal medullary slices after colinomimetic stimulation with acetylcholine, DMPP or nicotine. The in vivo effects of nicotine on the circulating plasma dopamine-beta-hydroxylase were tested in habitual and non habitual smokers after five cigarettes (12.5 mg of nicotine). The rise of plasma enzyme activity may reflect the increased catecholamine release from adrenal and peripheral adrenergic nerves.     

Blood carboxyhaemoglobin,plasma thiocyanate,and cigarette consumption: implications for epidemiological studies in smokers.

Carboxyhaemoglobin and plasma thiocyanate concentrations were found to be significantly correlated with self-reported daily cigarette consumption in 360 smokers (r = 0.416 and 0.412 respectively; p less than 0.001). The extent to which inhalation patterns affected the intake of cigarette smoke constituents was determined from the partial correlation between carboxyhaemoglobin and plasma thiocyanate concentrations after the number of cigarettes smoke per day had been allowed for (r = 0.48). Thus 23% of the variation in carboxyhaemoglobin and thiocyanate concentrations was accounted for by the was a cigarette was smoked and a further 21% by the number smoked a day. Furthermore, the relation between carboxyhaemoglobin or plasma thiocyanate and daily cigarette consumption was not linear but reached an asymptote at consumption rates above 25 cigarettes a day. These results suggest that by itself daily cigarette consumption will not identify those smokers most at risk and will also underestimate and dose-response relationship between smoking and selected diseases.     

Changes in pituitary responses to synthetic ovine corticotrophin releasing factor in fetal sheep

The rise in cortisol in fetal sheep during late pregnancy has been related to increased responsiveness of the adrenal to ACTH. Most reports have suggested that plasma ACTH concentrations rise coincident with or after the prepartum increase in cortisol. To reexamine the relationship of cortisol with basal immunoreactive ACTH (IR-ACTH) throughout the last 40 days of pregnancy and to determine changes in fetal pituitary responsiveness during this time, we measured basal and synthetic ovine corticotrophin-releasing factor (oCRF) (10 ng-10 micrograms) induced rises in ACTH and cortisol in fetal sheep at days 110-115, 125-130, and 135-140 of pregnancy. The fetuses were catheterized on day 105-120 and entered spontaneous labour at greater than 140 days. Basal IR-ACTH (picograms per millilitre +/- SEM) rose from 16.7 +/- 2.9 pg/mL at day 110-115 to 34.8 +/- 8.7 pg/mL at day 141-145. There was a significant effect of time on basal ACTH concentrations with a mean increase of approximately 5 pg ACTH per millilitre of plasma per 5-day sampling interval. Plasma cortisol changed gradually between day 110 and 125 of gestation and then more rapidly to term. At day 110-115 of gestation there was no significant change in plasma ACTH after 10 or 100 ng oCRF, but there was a significant increase in ACTH after 1 microgram of oCRF. Plasma cortisol did not change after any CRF injection. The change in IR-ACTH after oCRF at day 125-130 of gestation was significantly greater than that at day 110-115. Plasma cortisol concentrations were elevated following 1- and 10-micrograms injections of oCRF.(ABSTRACT TRUNCATED AT 250 WORDS)