Skip to main content
PMC home page
The BMJ logoLink to The BMJ
. 1988 Oct 15;297(6654):955–957. doi: 10.1136/bmj.297.6654.955

Vasoactive and atherogenic effects of cigarette smoking: a study of monozygotic twins discordant for smoking.

R Lassila 1, H W Seyberth 1, A Haapanen 1, H Schweer 1, M Koskenvuo 1, K E Laustiola 1
PMCID: PMC1834683  PMID: 3142565

Abstract

The mechanism by which atherosclerotic disease is induced by cigarette smoking has not yet been identified unequivocally. Chronic cigarette smoking and the generation of vasoactive prostanoids and the size of carotid atherosclerotic plaques were studied in nine pairs of identical male twins discordant for smoking for over 20 years. The urinary excretion of 2,3-dinor-thromboxane B2 (thromboxane B2 metabolite) of the smoking twin was significantly higher (on average 1.8 times higher) in every pair and that of 2,3-dinor-6-keto-prostaglandin F1 alpha (prostacyclin metabolite) was significantly higher (on average 1.3 times higher) in eight of the nine pairs. The ratio of excretion of these metabolites was significantly higher, being 4.0 (95% confidence interval 2.7 to 5.4) among the smokers compared with 2.9 (2.1 to 3.8) among the non-smokers, thus favouring a mechanism of vasoconstriction. Excretion of the thromboxane B2 metabolite was related to the urinary concentrations of nicotine metabolites. Atherosclerotic plaques detected by ultrasonography in the carotid arteries were significantly larger among smokers but did not correlate with the urinary excretion of prostacyclin and thromboxane B2 metabolites or intensity of smoking. Smoking was concluded to induce activation of platelets by an effect mediated by nicotine. The increased prostacyclin production, on the other hand, suggested a compensatory mechanism for the general vasoconstrictive properties of cigarette smoking.

Full text

PDF
955

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott R. D., Yin Y., Reed D. M., Yano K. Risk of stroke in male cigarette smokers. N Engl J Med. 1986 Sep 18;315(12):717–720. doi: 10.1056/NEJM198609183151201. [DOI] [PubMed] [Google Scholar]
  2. Baumgartner H. R., Sakariassen K. S. Factors controlling thrombus formation on arterial lesions. Ann N Y Acad Sci. 1985;454:162–177. doi: 10.1111/j.1749-6632.1985.tb11855.x. [DOI] [PubMed] [Google Scholar]
  3. Becker C. G., Dubin T., Wiedemann H. P. Hypersensitivity to tobacco antigen. Proc Natl Acad Sci U S A. 1976 May;73(5):1712–1716. doi: 10.1073/pnas.73.5.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caro C. G., Lever M. J., Parker K. H., Fish P. J. Effect of cigarette smoking on the pattern of arterial blood flow: possible insight into mechanisms underlying the development of arteriosclerosis. Lancet. 1987 Jul 4;2(8549):11–13. doi: 10.1016/s0140-6736(87)93052-2. [DOI] [PubMed] [Google Scholar]
  5. Cryer P. E., Haymond M. W., Santiago J. V., Shah S. D. Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. N Engl J Med. 1976 Sep 9;295(11):573–577. doi: 10.1056/NEJM197609092951101. [DOI] [PubMed] [Google Scholar]
  6. Davis J. W., Phillips P. E., Lewis H. D., Jr, Davis R. F. Relationships of the platelet aggregate ratio to serum cholesterol concentration, smoking and age. Postgrad Med J. 1981 Mar;57(665):150–152. doi: 10.1136/pgmj.57.665.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dzau V. J., Packer M., Lilly L. S., Swartz S. L., Hollenberg N. K., Williams G. H. Prostaglandins in severe congestive heart failure. Relation to activation of the renin--angiotensin system and hyponatremia. N Engl J Med. 1984 Feb 9;310(6):347–352. doi: 10.1056/NEJM198402093100603. [DOI] [PubMed] [Google Scholar]
  8. Falardeau P., Oates J. A., Brash A. R. Quantitative analysis of two dinor urinary metabolites of prostaglandin I2. Anal Biochem. 1981 Aug;115(2):359–367. doi: 10.1016/0003-2697(81)90018-x. [DOI] [PubMed] [Google Scholar]
  9. Fischer S., Bernutz C., Meier H., Weber P. C. Formation of prostacyclin and thromboxane in man as measured by the main urinary metabolites. Biochim Biophys Acta. 1986 Apr 15;876(2):194–199. doi: 10.1016/0005-2760(86)90274-2. [DOI] [PubMed] [Google Scholar]
  10. FitzGerald G. A., Pedersen A. K., Patrono C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation. 1983 Jun;67(6):1174–1177. doi: 10.1161/01.cir.67.6.1174. [DOI] [PubMed] [Google Scholar]
  11. FitzGerald G. A., Smith B., Pedersen A. K., Brash A. R. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N Engl J Med. 1984 Apr 26;310(17):1065–1068. doi: 10.1056/NEJM198404263101701. [DOI] [PubMed] [Google Scholar]
  12. Hallstrom A. P., Cobb L. A., Ray R. Smoking as a risk factor for recurrence of sudden cardiac arrest. N Engl J Med. 1986 Jan 30;314(5):271–275. doi: 10.1056/NEJM198601303140502. [DOI] [PubMed] [Google Scholar]
  13. Hartzell S. W., Byrne B. J., Subramanian K. N. Mapping of the late promoter of simian virus 40. Proc Natl Acad Sci U S A. 1984 Jan;81(1):23–27. doi: 10.1073/pnas.81.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hill P., Garbaczewski L. Gut-CNS peptide hormones, digestive dysfunction, and colon cancer. Nutr Cancer. 1987;10(1-2):11–22. doi: 10.1080/01635588709513936. [DOI] [PubMed] [Google Scholar]
  15. Hughson W. G., Mann J. I., Tibbs D. J., Woods H. F., Walton I. Intermittent claudication: factors determining outcome. Br Med J. 1978 May 27;1(6124):1377–1379. doi: 10.1136/bmj.1.6124.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jackson V. P., Bendick P. J. Duplex ultrasound screening for carotid arteriosclerotic disease in asymptomatic patients. J Ultrasound Med. 1985 Aug;4(8):411–415. doi: 10.7863/jum.1985.4.8.411. [DOI] [PubMed] [Google Scholar]
  17. Kaprio J., Sarna S., Koskenvuo M., Rantasalo I. The Finnish Twin Registry: formation and compilation, questionnaire study, zygosity determination procedures, and research program. Prog Clin Biol Res. 1978;24(Pt B):179–184. [PubMed] [Google Scholar]
  18. Klein L. W., Ambrose J., Pichard A., Holt J., Gorlin R., Teichholz L. E. Acute coronary hemodynamic response to cigarette smoking in patients with coronary artery disease. J Am Coll Cardiol. 1984 Apr;3(4):879–886. doi: 10.1016/s0735-1097(84)80344-7. [DOI] [PubMed] [Google Scholar]
  19. Lawson J. A., Brash A. R., Doran J., FitzGerald G. A. Measurement of urinary 2,3-dinor-thromboxane B2 and thromboxane B2 using bonded-phase phenylboronic acid columns and capillary gas chromatography--negative-ion chemical ionization mass spectrometry. Anal Biochem. 1985 Nov 1;150(2):463–470. doi: 10.1016/0003-2697(85)90536-6. [DOI] [PubMed] [Google Scholar]
  20. McMahan C. A., Richards M. L., Strong J. P. Individual cigarette usage: self-reported data as a function of respondent-reported data. Atherosclerosis. 1976 May-Jun;23(3):477–488. doi: 10.1016/0021-9150(76)90008-3. [DOI] [PubMed] [Google Scholar]
  21. Nadler J., Zipser R. D., Horton R. The effect of adrenergic stimulation on urinary prostaglandin E2 and 6 keto PGF1 alpha in man. Prostaglandins. 1983 Oct;26(4):519–530. doi: 10.1016/0090-6980(83)90190-9. [DOI] [PubMed] [Google Scholar]
  22. Nowak J., Murray J. J., Oates J. A., FitzGerald G. A. Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes. Circulation. 1987 Jul;76(1):6–14. doi: 10.1161/01.cir.76.1.6. [DOI] [PubMed] [Google Scholar]
  23. Packham M. A., Mustard J. F. The role of platelets in the development and complications of atherosclerosis. Semin Hematol. 1986 Jan;23(1):8–26. [PubMed] [Google Scholar]
  24. Peach H., Ellard G. A., Jenner P. J., Morris R. W. A simple, inexpensive urine test of smoking. Thorax. 1985 May;40(5):351–357. doi: 10.1136/thx.40.5.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pipili E., Poyser N. L. Release of prostaglandins I2 and E2 from the perfused mesenteric arterial bed of normotensive and hypertensive rats. Effects of sympathetic nerve stimulation and norepinephrine administration. Prostaglandins. 1982 Apr;23(4):543–549. doi: 10.1016/0090-6980(82)90114-9. [DOI] [PubMed] [Google Scholar]
  26. Pittilo R. M., Mackie I. J., Rowles P. M., Machin S. J., Woolf N. Effects of cigarette smoking on the ultrastructure of rat thoracic aorta and its ability to produce prostacyclin. Thromb Haemost. 1982 Oct 29;48(2):173–176. [PubMed] [Google Scholar]
  27. Schmidt K. G., Rasmussen J. W. Acute platelet activation induced by smoking. In vivo and ex vivo studies in humans. Thromb Haemost. 1984 Apr 30;51(2):279–282. [PubMed] [Google Scholar]
  28. Sonnenfeld T., Wennmalm A. Inhibition by nicotine of the formation of prostacyclin-like activity in rabbit and human vascular tissue. Br J Pharmacol. 1980;71(2):609–613. doi: 10.1111/j.1476-5381.1980.tb10980.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Strong J. P., Richards M. L. Cigarette smoking and atherosclerosis in autopsied men. Atherosclerosis. 1976 May-Jun;23(3):451–476. doi: 10.1016/0021-9150(76)90007-1. [DOI] [PubMed] [Google Scholar]
  30. Winniford M. D., Jansen D. E., Reynolds G. A., Apprill P., Black W. H., Hillis L. D. Cigarette smoking-induced coronary vasoconstriction in atherosclerotic coronary artery disease and prevention by calcium antagonists and nitroglycerin. Am J Cardiol. 1987 Feb 1;59(4):203–207. doi: 10.1016/0002-9149(87)90785-5. [DOI] [PubMed] [Google Scholar]
  31. Zimmerman M., McGeachie J. The effect of nicotine on aortic endothelium. A quantitative ultrastructural study. Atherosclerosis. 1987 Jan;63(1):33–41. doi: 10.1016/0021-9150(87)90079-7. [DOI] [PubMed] [Google Scholar]

Articles from BMJ : British Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES