Effect of chronic nicotine delivery on the proliferation rate of endothelial and smooth muscle cells in experimentally induced vascular wall plaques

Abstract

To study the effect of nicotine, cholesterol feeding, and their combination on endothelial and smooth muscle cells in vascular wall plaques an experimental method was established which allows the immunohistochemical detection and quantification of the fractions of endothelial and smooth muscle cells in DNA synthesis under the effect of these stimuli. For this purpose standardized fibromuscular plaques were produced by electrostimulation in the common carotid arteries of rabbits. The animals received either nicotine via implanted osmotic minipumps or a cholesterol diet or both. Plaque size was determined at the end of the experiments after 7 or 14 days as well as the fraction of endothelial and smooth muscle cells in DNA synthesis during exposure to bromodeoxyuridine (BrdU). The BrdU labeling index of endothelial cells clearly increased under chronic nicotine administration for either 7 days or 14 days compared to controls. The combination of nicotine and cholesterol diet led to a more significant increase. In contrast, the BrdU labeling index of smooth muscle cells was not increased under nicotine delivery. The combination of nicotine and cholesterol, however, led to a significant increase of the BrdU labeling index of smooth muscle cells in the plaques compared to cholesterol feeding. Measurement of the plaque size revealed no difference between controls and nicotine-treated animals after 14 days of nicotine delivery, whereas the combination of cholesterol and nicotine produced increased plaque formation compared to a group of animals which received a cholesterol diet alone.

Long-term nicotine exposure induces dysfunction of mouse endothelial progenitor cells

“…For example, a previous study investigating coronary heart disease identified smoking as one of the five key risk factors in development of atherosclerosis (20). In animal models, chronic nicotine treatment also increased the rate of development of atherosclerosis in arteries (21). Furthermore, nicotine in similar concentrations to those experienced by smokers impaired the structure and function of vascular smooth muscle and endothelial cells (22,23).…”

Effects of nicotine, its metabolites and tobacco extracts on human platelet function in vitro

“…By activating the sympathetic nervous system, nicotine induces increased heart rate and myocardial contraction, vasoconstriction in the skin and adrenal and neural release of catecholamines (Benowitz 1996). Nicotine can also affect lipid metabolism (Cluette-Brown et al, 1986), accelerate the development of atherosclerosis (Strohschneider et al, 1994) and induce endothelial dysfunction (Chalon et al, 2000). After entering the circulation, nicotine is subjected to extensive metabolism, resulting in a number of major and minor metabolites.…”

Effect of nicotine on cerebellar granule neuron development

“…For instance, in many in vitro studies, nAChR activation can increase cell proliferation, e.g., in a thymic cell line, lung cell carcinoma, subsets of normal and neoplastic cervical cells, neuroendocrine and vascular smooth muscle cells (Tominaga et al, 1989;Maneckjee & Minna, 1990;Quik et al, 1994;Strohschneider et al;1994;Waggoner & Wang, 1994;Carty et al, 1997). In contrast, several studies report that nicotine administration decreases rat brain DNA synthesis in several regions including the cerebellum McFarland et al, 1991;Slotkin et al, 1994), although one recent report suggests that increased numbers of mitotic neural cells are present in rat embryos exposed to nicotine in vitro (Roy et al, 1998).…”