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. 1981 Feb;102(2):229–238.

Effects of chronic oral consumption of nicotine on the rabbit aortic endothelium.

F M Booyse, G Osikowicz, A J Quarfoot
PMCID: PMC1903685  PMID: 7468769

Abstract

New Zealand white rabbits (10) were administered daily doses of nicotine (2.4 mg/kg/day) in their drinking water for 25 weeks. Nicotine-treated rabbits were compared with control rabbits (10) in terms of blood serum biochemistry and lipid profiles, blood cells counts, changes in aortic endothelial cell morphologic characteristic and distribution, and vessel wall permeability (Evans blue dye uptake). Fasting serum levels of glucose, triglycerides, total cholesterol, and LDL-cholesterol were elevated in nicotine-treated rabbits. No significant differences (nicotine vs control) were seen in leukocyte, erythrocyte and platelet counts, or hematocrit and hemoglobin. Control and nicotine-treated rabbit aortas showed similar focal areas of increased Evans blue dye uptake; staining was localized primarily to aortic arch areas. Endothelial cells (luminal surface) from non-Evans blue and Evans blue arch areas were examined by a combination of Häutchen preparation (silver-stained vessels) and scanning and transmission electron microscopy. Endothelial cells from nicotine-treated arch areas (Evans-blue-stained) showed extensive changes such as: increased cytoplasmic silver deposition, increased formation of microvilli, and numerous focal areas of "ruffled" endothelium (projections on cell surfaces). These data indicate that nicotine, administered orally to rabbits, has a demonstrable in vivo morphologic effect on endothelial cells in the aortic arch.

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Selected References

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

  1. Ahmed S. S., Moschos C. B., Lyons M. M., Oldewurtel H. A., Coumbis R. J., Regan T. J. Cardiovascular effects of long-term cigarette smoking and nicotine administration. Am J Cardiol. 1976 Jan;37(1):33–40. doi: 10.1016/0002-9149(76)90496-3. [DOI] [PubMed] [Google Scholar]
  2. Asmussen I., Kjeldsen K. Intimal ultrastructure of human umbilical arteries. Observations on arteries from newborn children of smoking and nonsmoking mothers. Circ Res. 1975 May;36(5):579–589. doi: 10.1161/01.res.36.5.579. [DOI] [PubMed] [Google Scholar]
  3. Auerbach O., Hammond E. C., Garfinkel L. Smoking in relation to atherosclerosis of the coronary arteries. N Engl J Med. 1965 Oct 7;273(15):775–779. doi: 10.1056/NEJM196510072731501. [DOI] [PubMed] [Google Scholar]
  4. Bizzi A., Tacconi M. T., Medea A., Garattini S. Some aspects of the effect of nicotine on plasma FFA and tissue triglycerides. Pharmacology. 1972;7(4):216–224. doi: 10.1159/000136292. [DOI] [PubMed] [Google Scholar]
  5. Boyle E., Jr, Morales I. B., Nichaman M. Z., Talbert C. R., Jr, Watkins R. S. Serum beta lipoproteins and cholesterol in men. Relationships to smoking, age and body weight. Geriatrics. 1968 Dec;23(12):102–111. [PubMed] [Google Scholar]
  6. Bálint A., Veress B., Jellinek H. Modifications of surface coat of aortic endothelial cells in hyperlipemic rats. Pathol Eur. 1974;9(2):105–108. [PubMed] [Google Scholar]
  7. Caplan B. A., Gerrity R. G., Schwartz C. J. Endothelial cell morphology in focal areas of in vivo Evans blue uptake in the young pig aorta. I. Quantitative light microscopic findings. Exp Mol Pathol. 1974 Aug;21(1):102–117. doi: 10.1016/0014-4800(74)90082-3. [DOI] [PubMed] [Google Scholar]
  8. Constantinides P., Robinson M. Ultrastructural injury of arterial endothelium. II. Effects of vasoactive amines. Arch Pathol. 1969 Aug;88(2):106–112. [PubMed] [Google Scholar]
  9. 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]
  10. DAWBER T. R., KANNEL W. B., REVOTSKIE N., STOKES J., 3rd, KAGAN A., GORDON T. Some factors associated with the development of coronary heart disease: six years' follow-up experience in the Framingham study. Am J Public Health Nations Health. 1959 Oct;49:1349–1356. doi: 10.2105/ajph.49.10.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DOYLE J. T., DAWBER T. R., KANNEL W. B., HESLIN A. S., KAHN H. A. Cigarette smoking and coronary heart disease. Combined experience of the Albany and Framingham studies. N Engl J Med. 1962 Apr 19;266:796–801. doi: 10.1056/nejm196204192661602. [DOI] [PubMed] [Google Scholar]
  12. DUGUID J. B. Pathogenesis of atherosclerosis. Lancet. 1949 Nov 19;2(6586):925–927. doi: 10.1016/s0140-6736(49)91503-2. [DOI] [PubMed] [Google Scholar]
  13. Fishman J. A., Ryan G. B., Karnovsky M. J. Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening. Lab Invest. 1975 Mar;32(3):339–351. [PubMed] [Google Scholar]
  14. French J. E. Atherosclerosis in relation to the structure and function of the arterial intima, with special reference to th endothelium. Int Rev Exp Pathol. 1966;5:253–353. [PubMed] [Google Scholar]
  15. Gerrity R. G., Richardson M., Caplan B. A., Cade J. F., Hirsh J., Schwartz C. J. Endotoxin-induced vascular endothelial injury and repair. II. Focal injury, en face morphology, (3H)thymidine uptake and circulating endothelial cells in the dog. Exp Mol Pathol. 1976 Feb;24(1):59–69. doi: 10.1016/0014-4800(76)90057-5. [DOI] [PubMed] [Google Scholar]
  16. Gerrity R. G., Schwartz C. J. Endothelial cell injury in early mild hypercholesterolemia. Prog Biochem Pharmacol. 1977;13:213–219. [PubMed] [Google Scholar]
  17. HAMMOND E. C. SMOKING IN RELATION TO MORTALITY AND MORBIDITY. FINDINGS IN FIRST THIRTY-FOUR MONTHS OF FOLLOW-UP IN A PROSPECTIVE STUDY STARTED IN 1959. J Natl Cancer Inst. 1964 May;32:1161–1188. [PubMed] [Google Scholar]
  18. Hladovec J. Endothelial injury by nicotine and its prevention. Experientia. 1978 Dec 15;34(12):1585–1586. doi: 10.1007/BF02034689. [DOI] [PubMed] [Google Scholar]
  19. Husain M. K., Frantz A. G., Ciarochi F., Robinson A. G. Nicotine-stimulated release of neurophysin and vasopressin in humans. J Clin Endocrinol Metab. 1975 Dec;41(06):1113–1117. doi: 10.1210/jcem-41-6-1113. [DOI] [PubMed] [Google Scholar]
  20. Isaac P. F., Rand M. J. Blood levels of nicotine and physiological effects after inhalation of tobacco smoke. Eur J Pharmacol. 1969 Dec;8(3):269–283. doi: 10.1016/0014-2999(69)90035-1. [DOI] [PubMed] [Google Scholar]
  21. JUERGENS J. L., BARKER N. W., HINES E. A., Jr Arteriosclerosis obliterans: review of 520 cases with special reference to pathogenic and prognostic factors. Circulation. 1960 Feb;21:188–195. doi: 10.1161/01.cir.21.2.188. [DOI] [PubMed] [Google Scholar]
  22. Kannel W. B., Castelli W. P., Gordon T. Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Ann Intern Med. 1979 Jan;90(1):85–91. doi: 10.7326/0003-4819-90-1-85. [DOI] [PubMed] [Google Scholar]
  23. Keys A., Taylor H. L., Blackburn H., Brozek J., Anderson J. T., Simonson E. Mortality and coronary heart disease among men studied for 23 years. Arch Intern Med. 1971 Aug;128(2):201–214. doi: 10.1001/archinte.1971.00310200037002. [DOI] [PubMed] [Google Scholar]
  24. Lewis J. C., Kottke B. A. Endothelial damage and thrombocyte adhesion in pigeon atherosclerosis. Science. 1977 May 27;196(4293):1007–1009. doi: 10.1126/science.860128. [DOI] [PubMed] [Google Scholar]
  25. McGILL H. C., Jr, GEER J. C., HOLMAN R. L. Sites of vascular vulnerability in dogs demonstrated by Evans blue. AMA Arch Pathol. 1957 Sep;64(3):303–311. [PubMed] [Google Scholar]
  26. Medalie J. H., Kahn H. A., Neufeld H. N., Riss E., Goldbourt U. Five-year myocardial infarction incidence. II. Association of single variables to age and birthplace. J Chronic Dis. 1973 Jun;26(6):325–349. doi: 10.1016/0021-9681(73)90036-2. [DOI] [PubMed] [Google Scholar]
  27. Murphy E. A., Mustard J. F. Tobacco and thrombosis. Am J Public Health Nations Health. 1966 Jul;56(7):1061–1073. doi: 10.2105/ajph.56.7.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mustard J. F., Packham M. A. The role of blood and platelets in atherosclerosis and the complications of atherosclerosis. Thromb Diath Haemorrh. 1975 Jun 30;33(3):444–456. [PubMed] [Google Scholar]
  29. POOLE J. C., SANDERS A. G., FLOREY H. W. The regeneration of aortic endothelium. J Pathol Bacteriol. 1958 Jan;75(1):133–143. doi: 10.1002/path.1700750116. [DOI] [PubMed] [Google Scholar]
  30. Richardson D. R., Morton R. F. Differential effects of chronic nicotine and tobacco smoke administration on iliac vascular resistance in the rat. Proc Soc Exp Biol Med. 1979 Jul;161(3):386–390. doi: 10.3181/00379727-161-40558. [DOI] [PubMed] [Google Scholar]
  31. Ross R., Glomset J. A. The pathogenesis of atherosclerosis (first of two parts). N Engl J Med. 1976 Aug 12;295(7):369–377. doi: 10.1056/NEJM197608122950707. [DOI] [PubMed] [Google Scholar]
  32. Sackett D. L., Gibson R. W., Bross I. D., Pickren J. W. Relation between aortic atherosclerosis and the use of cigarettes and alcohol. An autopsy study. N Engl J Med. 1968 Dec 26;279(26):1413–1420. doi: 10.1056/NEJM196812262792602. [DOI] [PubMed] [Google Scholar]
  33. Sharma H. M., Geer J. C. Experimental aortic lesions of acute serum sickness in rabbits. Am J Pathol. 1977 Aug;88(2):255–266. [PMC free article] [PubMed] [Google Scholar]
  34. Silkworth J. B., McLean B., Stehbens W. E. The effect of hypercholesterolemia on aortic endothelium studied en face. Atherosclerosis. 1975 Nov-Dec;22(3):335–348. doi: 10.1016/0021-9150(75)90015-5. [DOI] [PubMed] [Google Scholar]
  35. Spain D. M., Bradess V. A. Sudden death from coronary heart disease. Survival time, frequency of thrombi, and cigarette smoking. Chest. 1970 Aug;58(2):107–110. doi: 10.1378/chest.58.2.107. [DOI] [PubMed] [Google Scholar]
  36. Stefanovich V., Gore I., Kajiyama G., Iwanaga Y. The effect of nicotine on dietary atherogenesis in rabbits. Exp Mol Pathol. 1969 Aug;11(1):71–81. doi: 10.1016/0014-4800(69)90071-9. [DOI] [PubMed] [Google Scholar]
  37. Tulloss J. H., Booyse F. M. Effect of various agents and physical damage on giant cell formation in bovine aortic endothelial cell cultures. Microvasc Res. 1978 Jul;16(1):51–58. doi: 10.1016/0026-2862(78)90044-4. [DOI] [PubMed] [Google Scholar]
  38. WENZEL D. G., WATTANAPONGSIRI A., VEDRAL D. NICOTINE AND RENAL HYPERTENSION IN THE RAT. J Pharmacol Exp Ther. 1964 Sep;145:315–316. [PubMed] [Google Scholar]
  39. Weber G., Fabbrini P., Resi L. On the presence of a concanavalin-A reactive coat over the endothelial aortic surface and its modifications during early experimental cholesterol atherogenesis in rabbits. Virchows Arch A Pathol Pathol Anat. 1973 Jun 29;359(4):299–307. doi: 10.1007/BF00548601. [DOI] [PubMed] [Google Scholar]
  40. Wenzel D. G., Azmeh N. Chronically administered nicotine and the blood pressure of normotensive and renal hypertensive rats. Arch Int Pharmacodyn Ther. 1970 Oct;187(2):367–376. [PubMed] [Google Scholar]
  41. Worth R., Johnston D. G., Anderson J., Alberti K. G. Performance of blood-glucose strips. Lancet. 1979 Oct 6;2(8145):742–742. doi: 10.1016/s0140-6736(79)90667-6. [DOI] [PubMed] [Google Scholar]

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