Endothelium-Dependent and Endothelium-Independent Cerebral Vessel Reactions in a Chronic Smoking Model

Vera A. Nevzorova, PhD, ScD¹*, Natalia V. Zakharchuk, PhD¹, Tatiana R. Belushkina¹, Irina G. Agafonova, PhD², Evgeniy A. Gilifanov, PhD¹

¹Vladivostok State Medical University, Vladivostok, Russian Federation

²Pacific Institute of Bioorganic Chemistry, Far East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation

*Corresponding author: Prof. Vera A. Nevzorova, PhD, ScD, Vice Rector of Vladivostok State Medical University, 2, Ostryakov str., 690002, Vladivostok, Russian Federation. Tel.: 7- 4232-45-1702, Fax: 7-4232-45-1719. E-mail: nevzorova@inbox.ru


Objective: The aim of this study is to evaluate the endothelium-dependent and endothelium-independent reactions of the cerebral arteries in prolonged tobacco smoking settings reproduced in rat models in vivo.

Materials and Methods: To simulate the brain vascular pathology in smoking scenarios an experimental model of chronic smoking in rats has been reproduced in vivo. In this study, ten, 8-week-old Wistar male rats, weighing 310 to 350 g were used in the research. They were divided randomly into two groups. One group of four rats considered the control group, was exposed to breathing clean air, while the other group of six rats, termed the experimental group, was exposed to breathing cigarette smoke. Magnetic resonance imaging (MRI) of the brain was then performed to assess the level of change in the diameter of the cerebral arteries after the pharmacological stimuli were ascertained.

Conclusions: Prolonged cigarette smoking in rats results in the development of endothelial dysfunction in the cerebral vessels that is characterized by an impaired endothelial vasomotor level as a clear predominance of the abnormal constrictor responses. Two months post smoking cessation the vasomotor disturbances of the vascular endothelium of the rats were found to not only be preserved but also exacerbated by an increase in pathological vasoconstriction.

rats, cerebral vessel, chronic smoking.
  1. Global Programme on Evidence for Health Policy; WHO, World health Report, 2002.
  2. Guo X, Oldham MJ, Kleinman MT, Phalen RF, Kassab GS. Effect of cigarette smoking on nitric oxide, structural, and mechanical properties of mouse arteries. Am J Physiol Heart Circ Physiol 2006; 291(5): H2354 - H2361.
  3. Mahmud A, Feely J. Effect of Smoking on Arterial Stiffness and Pulse Pressure Amplification Hypertension 2003; 41: 183 – 187.
  4. Barnoya J. Glantz SA. Cardiovascular Effects of Secondhand Smoke: Nearly as Large as Smoking.  Circulation 2005; 111: 2684 – 2698.
  5. Guo X, Oldham MJ, Kleinman MT, et al. Effect of cigarette smoking on nitric oxide, structural, and mechanical properties of mouse arteries. Am J Physiol Heart Circ Physiol 2006; 291(5):2354 – 2361.
  6. Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMY 1989; 298: 789-94.
  7. Hongao Zheng, Yuening Liu, Tian Huang, Zheman Fang, Guishuang Li, Shaoheng He.  Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by side stream cigarette smoke. Toxicology Letters 2009; 189(3): 225–234.
  8. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288: 373–376.
  9. Marin J, Rodriges-Martinex MA. Role of vascular nitric oxide in physiological and pathological conditions. Pharmacol Ther 1997; 76:111-134.
  10.  Papamichael Ch M, Aznaouridis KA, Stamatelopoulos KS, Karatzis EN, Protogerou AD, Papaioannou ThG, et al. Endothelial dysfunction and type of cigarette smoked: the impact of 'light' versus regular cigarette smoking. Vascular Medicine 2004; 9: 103-105.
  11.  Zeiher АM, Schachinger V, Мinnen F. Long-term cigarette smoking impairs endothelium independent coronary arterial vasodilator function. Circulation 1995; 92: 1094–100.
  12.  Vane JR, Anggard EE, Batting RM.  Regulatory functions of the vascular endothelium. New Engl Med 1990; 323:27-36.
  13. Busse R , Mulsch A, Fleming I, Hecker M.  Mechanisms of nitric oxide release from the vascular endothelium. Circulation 1993; 87: 18-26.
  14.  Celermajer DS, Sorensen KE, Georgakopoulos D, Bull S, Thomas O, Robinson J, et al. Cigarette smoking is associated with dose – related and potentially reversible impairment of endothelium -dependent dilation in healthy young adults. Circulation 1993; 88: 2149—2155.
  15.  Miyazaki H, Matsuoka H, Cooke IP, Usui M, Ueda S, Okuda S, et al. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999; 99:1141-1146.
  16.  Liu Y, Lee K, Perez-Padilla R, Hudson NL, Mannino DM. Outdoor and indoor air pollution and COPD-related diseases in high- and low-income countries.  Int J Tuberc Lung Dis 2008; 12(2):115-27.

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Int J Biomed. 2011; 1(2):103-107.© 2011 International Medical Research and Development Corporation. All rights reserved.