Upper airway cooling and l-menthol reduce ventilation in the guinea pig

Orani, G. P.; Anderson, James W.; Sant'Ambrogio, G.; Sant'Ambrogio, F.B.

doi:10.1152/jappl.1991.70.5.2080

Cited by 80 publications

(44 citation statements)

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“…Menthol is known to stimulate cold receptors and to produce a cooling sensation as well as local anesthesia. In animals, menthol inhalation results in longer air retention time in the lungs (Orani et al, 1991;Sant'Ambrogio et al, 1991). Furthermore, many African-Americans report the ease of inhalation and ability to inhale more deeply as reasons for smoking mentholated cigarettes (Hymowitz et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Mentholated Cigarette Smoking Inhibits Nicotine Metabolism

Benowitz¹,

Herrera²,

Jacob³

2004

J Pharmacol Exp Ther

220

161

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Smoking mentholated cigarettes has been suggested to convey a greater cancer risk compared with smoking nonmentholated cigarettes. Two of the possible mechanisms by which mentholated cigarette smoking could increase risk are by increasing systemic exposure to tobacco smoke toxins and by affecting the metabolism of nicotine or tobacco smoke carcinogens. To examine these possibilities, we performed a crossover study in 14 healthy smokers, one-half of whom were African-Americans and one-half whites. Subjects were randomly assigned to smoke mentholated or nonmentholated cigarettes for 1 week, then to cross over to the other type of cigarettes for another week. Subjects were confined to a Clinical Research Center for 3 days of each week, during which time blood levels of nicotine and carbon monoxide were measured throughout the day and an intravenous infusion of deuterium-labeled nicotine and cotinine was administered to determine the rate and pathways of nicotine metabolism. The systemic intake of nicotine and carbon monoxide was, on average, not affected by mentholation of cigarettes. Mentholated cigarette smoking did significantly inhibit the metabolism of nicotine (clearance: 1289 versus 1431 ml/min, two sided, p ϭ 0.02). Inhibition of nicotine metabolism occurred both by slower oxidative metabolism to cotinine and by slower glucuronide conjugation. Our data do not support the hypothesis that mentholated cigarette smoking results in a greater absorption of tobacco smoke toxins. Our finding of impaired metabolism of nicotine while mentholated cigarette smoking suggests that mentholated cigarette smoking enhances systemic nicotine exposure.

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Section: Discussionmentioning

confidence: 99%

Mentholated Cigarette Smoking Inhibits Nicotine Metabolism

Benowitz¹,

Herrera²,

Jacob³

2004

J Pharmacol Exp Ther

220

161

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“…UA cooling inhibits breathing in adult cats [5], guineapigs [25] and rats [7], and also in neonatal dogs [26] and guinea-pigs [12]. On the other hand, laryngeal cooling has no effect on breathing in adult dogs [3]; and JAMMES et al [4] observed no significant changes in ventilation with laryngeal cooling in adult cats.…”

Section: Discussionmentioning

confidence: 99%

Effect of upper airway cooling and CO2 on diaphragm and geniohyoid muscle activity in the rat

O’Halloran¹,

Curran²,

Bradford³

1996

Eur Respir J

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E Ef ff fe ec ct t o of f u up pp pe er r a ai ir rw wa ay y c co oo ol li in ng g a an nd d C CO O 2 2 o on n d di ia ap ph hr ra ag gm m a an nd d g ge en ni io o--h hy yo oi id d m mu us sc cl le e a ac ct ti iv vi it ty y i in n t th he e r ra at t Diaphragm and geniohyoid electromyographic activities were recorded in anaesthetized rats, breathing spontaneously through a low-cervical tracheostomy. Warmed, humidified air containing 0 or 10% CO 2 and cooled, room humidity air were applied at constant flow to the UA through a high-cervical tracheostomy. Spontaneous tracheal airflow, UA airflow and temperature, blood pressure, and rectal temperature were recorded.In all animals, the geniohyoid muscle had phasic inspiratory activity, which slightly preceded diaphragmatic activity. CO 2 had no effect on mean peak integrated diaphragmatic activity and variable effects on geniohyoid activity. The coefficients of variation of these activities were unaffected by CO 2 . Similar results were obtained following bilateral mid-cervical vagotomy. Cool air decreased respiratory frequency (78±8%) (mean±SD % of control), peak inspiratory flow (78±5%) and diaphragmatic activity (77±4%), and increased geniohyoid activity (149±11%). Cutting the superior laryngeal nerves abolished these effects.In conclusion, whilst moderate upper airway cooling inhibits breathing and excites geniohyoid muscle activity, upper airway carbon dioxide has minimal effect. Eur Respir J., 1996Respir J., , 9, 2323 Cooling of the upper airway (UA) stimulates laryngeal cold receptors [1] and inhibits laryngeal mechanoreceptors [2] running in the superior laryngeal nerve (SLN). These receptors are known to reflexly influence breathing and UA muscle activity, but the effects of cooling on UA muscle activity are controversial. In anaesthetized dogs, MATHEW et al. [3] found that laryngeal cooling (20-25°C) had no effect on posterior cricoarytenoid muscle activity but inhibited the muscle's response to UA occlusion, and this effect was abolished by SLN section. In anaesthetized cats, JAMMES et al. [4] reported that laryngeal cooling (8°C) inhibited laryngeal muscle activity (the identity of the muscle was not determined) but the effect of SLN section on this response was not examined. On the other hand, UKABAM et al. [5], in decerebrate, vagotomized cats, found that hypoglossal nerve activity was either excited or inhibited by laryngeal cooling (8-16°C) through a SLN-mediated reflex. The cause of these conflicting results may be due to whether the vagi were intact or cut, since vagal afferents greatly influence UA muscle activity [6], or else it may be related to the low and wide-ranging temperatures used. In anaesthetized rats, we have previously shown that more moderate cooling (25-30°C) of the UA causes a substantial fall in UA resistance, which is partly mediated through a SLN reflex [7]. The mechanism of this effect is unknown but we have speculated that it may be due to reflex activation of UA dilator muscles.The application of CO 2 to the UA in cats has ...

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“…Menthol stimulates cold receptors, with the resulting sensation of coolness perceived not only in the mouth and pharynx but also in the lungs (Eccles, 1994(Eccles, , 2000. Stimulation of laryngeal cold receptors may reduce airway irritation (Orani, Anderson, Sant'Ambrogio, & Sant'Ambrogio, 1991). This sensation of coolness might result in deeper inhalation, but because of the difficulty in precisely measuring the inhalation phase of smoking, this issue has not been studied adequately.…”

Section: Why It Is Important To Study Menthol Cigarettesmentioning

confidence: 99%