Basal Release of EDRF under Conditions of Oxidant Stress
Tremendous progress has been made in our understanding of the nature as well as the mechanisms of generation and release of endothelium-derived relaxing factor (EDRF) since the milestone discovery of Furchgott and colleagues concerning the central role of endothelium in regulating vascular tone (Furchgott and Zawadzki, 1980). It is now evident that nitric oxide (NO) generated within the endothelial cells from the guanidino nitrogen atom of L-arginine via the constitutive activity of nitric oxide synthase (cNOS) conveys a variety of messages to maintain the fluidity of the blood, to prevent adhesion and aggregation of platelets and to determine the tone of the vessel wall by relaxing vascular smooth muscle ((Furchgott, 1988; Ignarro et al, 1988; Palmer et al, 1987; Bredt et al, 1991, Förstermann et al, 1991; Radomski et al, 1987). Although the release of EDRF was initially described as a mode of action of pharmacological agents commonly acting on the surface of endothelial cells and increasing intracellular free calcium levels, agonist-independent formation, release and action of EDRF has recently also received considerable attention. Basal release of nitrogen oxides has been observed from cultured endothelial cells, and the ability of the endothelium to respond with increased EDRF output to mechanical stimuli such as pulsatility and increased blood flow has been demonstrated (Schmidt et al., 1990; Myers et al., 1989; Rubanyi et al., 1986). The introduction of specific inhibitors of endothelial NO synthesis proved to be an especially useful tool to delineate the in vivo activity and function of such NO regulation.
KeywordsSuperoxide Thiol Catalase Cardiol Acetylcholine
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