3. Conclusion

Pharmacological tests caused expected endothelium-dependent and endothelium-independent vasodilation in healthy rats proving that NO synthase and GC mechanisms of vascular endothe-

Data are presented as mean SD. \*p < 0.05 (t-test analysis was used to assess the differences in the values) in comparison with the control group. EDVD, endothelium-dependent vasodilation; EIDVD, endothelium-independent vasodilation; EDVC, endothelium-dependent vasoconstriction; EIDVC, endothelium endothelium-independent vasoconstriction; %,

Descriptor Control (rats, N = 10) Tobacco smoking (rats, N = 12)

EDVD, % +11.89 0.98 0.64 0.02\* EIDVD, % +17.84 1.25 + 8.64 0.76\* EDVC, % 6.31 0.14 +5.95 0.34\* EIDVC, % 4.83 0.12 11.2 1.01\*

At the same time, our results showed significant differences in vasomotor reactions of rats exposed to tobacco smoking. ACh stimulates eNOS causing NO secretion that results in pronounced EDVD [58]. Our results showed that the control group of rats exhibited an expected, sufficient level of EDVD in their brain vessels. Furthermore, arterial diameter increased by more than 10% of the original level in healthy rats indicating that the Enos-mediated mechanism of

Alternatively, the group of smokers had pathological vasospastic reactions after ACh administration (Table 3). The reason might be related to functional damage of vascular endothelium. Some experiments showed that chronic exposure to tobacco smoke causes NO deficiency and weaker activity of eNOS [59, 60]. Based on previous mechanistic reports [53–55], we can assume that there is an NO deficiency and lower level of endothelial eNOS activity in our model of tobacco smoking that indicates substantial damage of eNOS mechanism and thus

Apart from the eNOS mechanism of vasodilation, there is also another one involving GC. NO molecule is a highly active radical due to its unpaired electron. Its chemical properties allow it to access vascular myocytes and activate intracellular GC without any receptors. As a result, the cell concentration of cGMP becomes higher, and smooth muscle cells relax [61, 62]. GC mechanism of vasodilation was studied by injecting rats with nitroglycerin as the NO donor. The control group of rats had an expected level of EIDVD induced by nitroglycerin. In addition, arterial diameter increases by more than 15% of the original level indicates that GC endothelium-independent mechanism of vasodilation in healthy rats remained intact [63]. Chronic smokers' group had insufficient vasodilation after the same stimulation that indicates damages in both eNOS and GC mechanisms of vasodilation in animal smokers. Some authors believe that weaker response of vascular smooth muscle cells to nitrovasodilators might be

Analysis of the constricting section in the smokers' group shows pathological vasodilation in response to L-NMMA constrictor administration and pronounced constriction after norepinephrine

initiated by hypoxia that exists in long-term smoking [52, 64–66].

lium dilation remained intact [57].

percent change after the appropriate tests.

Table 3. Vasomotor function of cerebral arteries in smoking.

318 Endothelial Dysfunction - Old Concepts and New Challenges

vasodilation remained intact (Table 3).

impaired vasodilation.

Endothelium initiates and modulates the main pathomorphological processes of chronic respiratory diseases. In particular, endothelium activation is an important factor of initiation, development and persistence of inflammation and vessels and tissue remodeling; it contributes to lymph circulation dysfunction and development of systemic effects. Endothelial cells of different vessels are morphologically and functionally oriented toward optimal regulation of organs' blood supply by synthesizing and releasing locally acting mediators. Pathology of endothelial cells can develop selectively: the cells are sensitive to hypoxia, tobacco smoke influence, products of inflammatory response, peroxidation, ischemic disorders, swelling and so on. Vessel remodeling usually starts as adaptation to hemodynamic changes or activity of tissue and circulating humoral factors. Long-term adaptation is replaced by vessel structure deterioration as a response to damaging factors, including toxic components of tobacco smoke and metabolites and atherogenic factors or changes of hemodynamic load. Cognitive dysfunction in cases of chronic nicotine-associated diseases is recognized by the majority of medical experts as one of the systemic symptoms of such diseases and a big medical and socioeconomic challenge. Studying the peculiarities of endothelium dysfunction caused by chronic exposure to tobacco smoke is relevant for finding a way of treating progressing cognitive deficiency and developing personalized methods of preventing acute vascular events.

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