Abstract
The effects of smoking cessation with and without nicotine substitution on prostaglandin E2, leukotriene B4, leukotriene E4, and thromboxane B2 synthesis ex vivo in man were investigated. Blood samples were obtained from 20 healthy non-smoking controls and from 30 healthy smoking volunteers before and 3, 7 and 14 days after smoking cessation. Half of the smokers used nicotine chewing gum as a substitution therapy. Urinary cotinine and trans-3′-hydroxycotinine as well as thiocyanate excretions were used as indicators for the use of nicotine chewing gum and smoking, respectively. Prostaglandin E2, leukotriene E4, and thromboxane B2 were measured from whole blood after calcium ionophore A23187 stimulation by direct radioimmunoassay and leukotriene B4 by RP-HPLC.
Prostaglandin E2 and thromboxane B2 syntheses were about three times and leukotriene B4 and E4 syntheses four times higher in smokers than in controls. Three days after smoking cessation without nicotine substitution, levels were lowered significantly to about 70%, 80%, 45% and 60% of the initial values; and after 14 days to 55%, 80%, 45% and 50%, respectively. In the nicotine substitution group no significant decreases were seen during the two-week follow-up.
The increased level of eicosanoid synthesis detected in smokers in this ex vivo study may contribute to the harmful cardiovascular effects of smoking. Long-term nicotine substitution might diminish the beneficial effects of smoking cessation due to the possible stimulatory effects of nicotine and cotinine on eicosanoid synthesis even in vivo.
Similar content being viewed by others
References
Alanko J, Riutta A, Vapaatalo H, Mucha I (1991) Catecholamines decrease leukotriene B4 and increase thromboxane B2 synthesis in A23187-stimulated human whole blood. Prostaglandins 42:279–287
Alanko J, Riutta A, Mucha I, Kerttula T, Kaukinen S, Vapaatalo H, Metsä-Ketelä T, Seppälä E (1992) Adrenaline stimulates thromboxane and inhibits leukotriene synthesis in man. Eicosanoids 5:169–175
Barrow SE, Ward PS, Sleightholm MA, Ritter JM, Dollery CT (1989) Cigarette smoking: profiles of thromboxane- and prostacyclin-derived products in human urine. Biochim Biophys Acta 993:121–127
Benowitz NL (1988) Pharmacologic aspects of cigarette smoking and nicotine addiction. N Engl J Med 319:1318–1330
Benowitz NL (1991) Nicotine and coronary heart disease. Trends Cardiovasc Med 1:315–321
Blache D, Bouthillier D, Davignon J (1992) Acute influence of smoking on platelet behaviour, endothelium and plasma lipids and normalization by aspirin. Atherosclerosis 93:179–188
Bridges AB, Hill A, Belch JJF (1993) Cigarette smoking increases white blood cell aggregation in whole blood. J Roy Soc Med 86:139–140
de Gaetano G, Evangelista V; Rajtar G, Del Maschio A, Cerletti C (1990) Activated polymorphonuclear leukocytes stimulate platelet function. Thromb Res Suppl XI:25–32
Dobson AJ, Alexander HM, Heller RF, Lloyd DM (1991) How soon after quitting smoking does risk of heart attack decline? J Clin Epidemiol 44:1247–1253
Giraudi G, Grillo C (1981) Direct spectrophotometric determination of thiocyanate in serum and urine with a continuous-flow analyzer. Anal Chim Acta 128:169–175
Gresele P, Arnout J, Coene MC, Deckmyn H, Vermylen J (1986) Leukotriene B4 production by stimulated whole blood: comparative studies with isolated polymorphonuclear cells. Biochem Biophys Res Commun 137:334–342
Henriksson P, Rasmanis G, Edhag O, Vesterqvist O, Gréen K (1990) Thromboxane synthase inhibition: “endoperoxide shunt phenomenon” does not occur in healthy humans in vivo. Prostaglandins 39:99–107
Höfer I, Nil R, Wyss F, Bättig K (1992) The contributions of cigarette yield, consumption, inhalation and puffing behaviour to the prediction of smoke exposure. Clin Invest 70:343–351
Jackson M (1993) Cerebral arterial narrowing with nicotine patch. Lancet 342:236–237
Kobayashi J, Kihira Y, Kitamura S (1988) Effects of cigarette smoking on blood levels of leukotrienes and plasma levels of complements C3a and C5a in healthy volunteers. Arch Env Health 43:371–374
Michiels C, Arnould T, Knott I, Dieu M, Remacle J (1993) Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. Am J Physiol 264 (Cell Physiol 33):C866–874
Palmer KJ, Buckley MM, Faulds D (1992) Transdermal nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Drugs 44:498–529
Parviainen MT, Barrow RD (1988) Assessment of exposure to environmental tobacco smoke using a high-performance liquid chromatographic method for the simultaneous determination of nicotine and two of its metabolites in urine. J Chromatog 431:216–221
Racké K, Schwörer H (1992) Nicotinic and muscarinic modulation of 5-hydroxytryptamine (5-HT) release from porcine and canine small intestine. Clin Invest 70:190–200
Racké K, Schwörer H, Simson G (1992) Effects of cigarette smoking or ingestion of nicotine on platelet 5-hydroxytryptamine (5-HT) levels in smokers and non-smokers. Clin Invest 70:201–204
Rennard SI, Daughton D, Fujita J, Oehlerking MB, Dobson JR, Stahl MG, Robbins RA, Thompson AB (1990) Short-term smoking reduction is associated with reduction in measures of lower respiratory tract inflammation in heavy smokers. Eur Respir J 3:752–759
Rival J, Riddle JM, Stein PD (1987) Effects of chronic smoking on platelet function. Thromb Res 45:75–85
Saareks V, Riutta A, Mucha I, Alanko J, Vapaatalo H (1993) Nicotine and cotinine modulate eicosanoid production in human leukocytes and platelet rich plasma. Eur J Pbarmacol 248:345–349
Shappel SB, Taylor AA, Hughes H, Mitchell JR, Andersson DC, Smith CW (1990) Comparison of antioxidant and nonantioxidant lipoxygenase inhibitors on neutrophil function. Implication for pathogenesis of myocardial reperfusion injury. J Pharmacol Exp Ther 252:531–538
Sih CJ, Takeguchi C, Foss P (1970) Mechanism of prostaglandin biosynthesis. III. Catecholamines and serotonin as coenzymes. J Am Chem Soc 92:6670
Thornton WH Jr, Adelstein EH, Edes TE (1989) Leukotriene B4 is measurable in serum of smokers and nonsmokers. Clin Chem 35:459–460
Verbeuren TJ (1989) Synthesis, storage, release and metabolism of 5-hydroxytryptamine in peripheral tissues. In: Fozard JR (ed) Peripheral actions of 5-hydroxytryptamine. Oxford University Press, Oxford, pp 1–25
Wennmalm A, Benthin G, Caidahl K, Granström EF, Lanne B, Persson L, Petersson A-S, Winell S (1990) Non-invasive assessment of the cardiovascular eicosanoids, thromboxane A2 and prostacyclin, in randomly sampled males, with special reference to the influence of inheritance and environmental factors. Clin Sci 79:639–645
Wennmalm A, Benthin G, Granström EF, Persson L, Petersson A-S, Winell S (1991) Relation between tobacco use and urinary excretion of thromboxane A2 and pros,tacyclin metabolites in young men. Circulation 83:1698–1704
Zakrzewski JT, Sampson AP, Evans JM, Barnes NC, Piper PJ, Costello JF (1989) The biotransformation in vitro of cysteinyl leukotrienes in blood of normal and asthmatic subjects. Prostaglandins 37:425–444
Zijlstra FJ, Vincent JE, Mol WM, Hoogsteden HC, Van Halt PThW, Jongejan RC (1992) Eicosanoid levels in bronchoalveolar lavage fluid of young female smokers and non-smokers. Eur J Clin Invest 22:301–306
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Riutta, A., Saareks, V., Mucha, I. et al. Smoking cessation and nicotine substitution modulate eicosanoid synthesis ex vivo in man. Naunyn-Schmiedeberg's Arch Pharmacol 352, 102–107 (1995). https://doi.org/10.1007/BF00169196
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169196