1. Introduction

Vascular endothelium initiates and actively participates in inflammatory reactions in the majority of chronic respiratory diseases. Endothelial dysfunction (ED) that develops as clinically

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

manifested disruptions of endothelium-dependent vasomotor reactions on local and systemic levels related with inflammation of different genesis should be regarded as a major segment of the cardiorespiratory continuum. Endothelium can autonomously produce at least 20 biologically active substances that are synthesized and released depending on current functional requirements. Endothelium functions create a balance of regulatory substances that determine the whole operation of interaction and control system (Figure 1). They include factors that are responsible for contraction and relaxation of smooth muscles in vessel walls, coagulation and fibrinolysis, control of cell proliferation and apoptosis, regulating the reaction to foreign substances and facilitating interaction with lymph vessels and drainage.

Today there is a substantial amount of evidence proving the endothelium involvement in development of local and systemic damage from tobacco smoke that is an indisputable cause of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), some phenotypes of asthma, idiopathic pulmonary fibrosis and so on [2, 7, 8, 20]. The correlation between the intensity of tobacco smoking and rapid decline in lung function is a proven fact. According to WHO, tobacco smokers experience sudden death five times more frequently than non-smokers [1]. The mechanisms of damage done to the blood vessels induced by tobacco combustion products have not been studied extensively at the moment, even though it is accepted that tobacco does not have any exclusive ways of producing vascular damage. Nicotine being the main component of tobacco smoke stimulates catecholamine release leading to stimulation of β1 and β2 adrenoreceptors. Nicotine induces a degradation of nitric oxide (NO) [2]. NO induces vasodilation by stimulating soluble guanylate cyclase (GC) to produce cyclic guanosine monophosphate (cGMP) [3]. Thus, nicotine causes change of reactions during vasodilatation. Apart from nicotine, tobacco smoke includes 4000 chemical substances, 100 of them having various toxic effects along with antigenic, cytotoxic, mutagenic and carcinogenic properties [4, 5]. They are able to interfere with cellular structure and processes of intercellular signaling by stimulating apoptosis, lipid peroxidation in cellular membrane, DNA and RNA strings' rupture and mitochondrial respiratory chain disruption. Tobacco smoke components are not the only factors directly responsible for stimulating and damaging endothelium in case of respiratory diseases; there are also endogenous factors, such as cellular and non-cellular inflammation mediators, bacterial toxins, immune complexes, hypoxemia, free radicals and

Smoking, Respiratory Diseases and Endothelial Dysfunction

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In general, the sequence of events altering functional properties of endothelium can be described as follows. Damaging factors (different in nature, intensity and length) activate and/or damage endothelium gradually exhausting its compensation abilities and leading to abnormal (altered) response to the same damaging factors and even to regular stimuli. It results in prolonged vasoconstriction, higher adhesion and clotting level, weakened barrier function, intensification of cellular proliferation and some other consequences with certain clinical symptoms: vascular hypertension, swelling, vascular remodeling and so on. In addition, some effects, including those related to renin-angiotensin system and endothelial involvement in inflammation process, are

2. Respiratory diseases and cerebral vascular endothelial dysfunction

According to modern conceptions, the central nervous system is an important participant in the pathogenesis of a number of chronic respiratory diseases, including those having a nicotineassociated nature. An important regulator of hemoperfusion of the brain is the vascular endothelium [8]. There are specific endothelium-dependent reactions in the arteries of the brain [9, 15]. Cerebral autoregulation maintains constant blood flow (CBF) through the brain in spite of changing mean arterial pressure. Autoregulation of cerebral blood flow consists of mechanoand chemoregulation. Chemoregulation is in direct correlation to the serum level of carbon dioxide and is, contrary to mechanoregulation, independent of changes in mean arterial pressure.

shear stress alteration in endothelium [6–12].

both local and systemic nature.

Figure 1. Functional processes balance in normal endothelial function.

Today there is a substantial amount of evidence proving the endothelium involvement in development of local and systemic damage from tobacco smoke that is an indisputable cause of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), some phenotypes of asthma, idiopathic pulmonary fibrosis and so on [2, 7, 8, 20]. The correlation between the intensity of tobacco smoking and rapid decline in lung function is a proven fact. According to WHO, tobacco smokers experience sudden death five times more frequently than non-smokers [1]. The mechanisms of damage done to the blood vessels induced by tobacco combustion products have not been studied extensively at the moment, even though it is accepted that tobacco does not have any exclusive ways of producing vascular damage. Nicotine being the main component of tobacco smoke stimulates catecholamine release leading to stimulation of β1 and β2 adrenoreceptors. Nicotine induces a degradation of nitric oxide (NO) [2]. NO induces vasodilation by stimulating soluble guanylate cyclase (GC) to produce cyclic guanosine monophosphate (cGMP) [3]. Thus, nicotine causes change of reactions during vasodilatation. Apart from nicotine, tobacco smoke includes 4000 chemical substances, 100 of them having various toxic effects along with antigenic, cytotoxic, mutagenic and carcinogenic properties [4, 5]. They are able to interfere with cellular structure and processes of intercellular signaling by stimulating apoptosis, lipid peroxidation in cellular membrane, DNA and RNA strings' rupture and mitochondrial respiratory chain disruption. Tobacco smoke components are not the only factors directly responsible for stimulating and damaging endothelium in case of respiratory diseases; there are also endogenous factors, such as cellular and non-cellular inflammation mediators, bacterial toxins, immune complexes, hypoxemia, free radicals and shear stress alteration in endothelium [6–12].

manifested disruptions of endothelium-dependent vasomotor reactions on local and systemic levels related with inflammation of different genesis should be regarded as a major segment of the cardiorespiratory continuum. Endothelium can autonomously produce at least 20 biologically active substances that are synthesized and released depending on current functional requirements. Endothelium functions create a balance of regulatory substances that determine the whole operation of interaction and control system (Figure 1). They include factors that are responsible for contraction and relaxation of smooth muscles in vessel walls, coagulation and fibrinolysis, control of cell proliferation and apoptosis, regulating the reaction to foreign sub-

stances and facilitating interaction with lymph vessels and drainage.

308 Endothelial Dysfunction - Old Concepts and New Challenges

Figure 1. Functional processes balance in normal endothelial function.

In general, the sequence of events altering functional properties of endothelium can be described as follows. Damaging factors (different in nature, intensity and length) activate and/or damage endothelium gradually exhausting its compensation abilities and leading to abnormal (altered) response to the same damaging factors and even to regular stimuli. It results in prolonged vasoconstriction, higher adhesion and clotting level, weakened barrier function, intensification of cellular proliferation and some other consequences with certain clinical symptoms: vascular hypertension, swelling, vascular remodeling and so on. In addition, some effects, including those related to renin-angiotensin system and endothelial involvement in inflammation process, are both local and systemic nature.
