Eicosanoids vascular smooth muscle

Some of the biologic effects of certain eicosanoids occur as a result of a paracrine or autocrine action. One paracrine action is the contraction of vascular smooth muscle cells caused by TXA2 released from circulating platelets (vasoconstriction). An autocrine action of eicosanoids is exemplified by platelet aggregation induced by TXA2 produced by the platelets themselves. 

Coronary heart disease and atherosclerosis are major contributors to morbidity and mortality in the United States and other developed countries. Epidemiological studies suggest that decreased mortality from coronary heart disease is associated with moderate consumption of alcohol, and especially of red wine [7], Numerous studies indicate that resveratrol inhibits platelet aggregation [8-10, 12, 16, 54, 55], alters eicosanoid synthesis [15, 55], modulates lipoprotein mechanisms [14, 56-58], inhibits vascular smooth muscle cell proliferation [59], and acts as an estrogen receptor agonist [60]. On the other hand, at least one earlier study indicated that it promoted atherosclerotic development, rather than protected against it, by a mechanism that appeared to be independent of observed... 

Sun J, Sui X, Bradbury JA, Zeldin DC, Conte MS, Liao JK (2002) Inhibition of vascular smooth muscle cell migration by cytochrome p450 epoxygen-ase-deiived eicosanoids. Circ Res 90 1020-1027... 

Mechanism of the Effects of Eicosanoids on Vascular Smooth Muscle. 25... 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

Being an anaphylatoxin, however, C5a also expresses many proinflammatory activities. These include its potent chemotactic activities for the recruitment of inflammatory cells to sites of tissue injury and infection (Shin et al., 1968), its ability to induce smooth muscle contraction (Hugh et al., 1987), increase vascular permeability (Hugh and Muher-Eberhard, 1978 Hugh, 1981, 1990), and induce the release of a variety of secondary inflammatory mediators such as histamine, lysosomal enzymes, and vasoacdve eicosanoids from responsive cells such as mast cells, neutrophils, eosinophils, and macrophages (Drapeau etal., 1993 Johnson et al., 1975 Goldstein and Weissmann, 1974 Schorlemmer et al., 1976 Lundberg et al., 1987). 

Glucocorticoids do not directly relax airway smooth muscle and thus have little effect on acute bronchoconstriction. Their anti-inflammatory effects in asthma include modulation of cytokine and chemokine production inhibition of eicosanoid synthesis marked inhibition of accumulation of basophils, eosinophils, and other leukocytes in lung tissue and decreased vascular permeability. Because of their profound and generalized anti-inflammatory actions, glucocorticoids are the most effective drugs used in the treatment of asthma. 

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