Oxygen Radical Regulation of Vascular Reactivity
Lipid peroxides are implicated in the pathophysiology of many disease processes including cancer, atherosclerosis and inflammation (Frankel 1984). Several mechanisms have been suggested for these peroxide mediated events. These include loss of membrane integrity, liberation of lysosomal enzymes and initiation of destructive free radical mediated reactions (Bridges et al. 1983; Mak et al. 1983). However, the actual mechanism is still unknown. Enhanced Prostaglandin synthesis occurs in human tumours. This may relate to the stimulation of Prostaglandin H (PGH) synthetase by lipid peroxides (Hemler and Lands 1980). On the other hand lipid peroxides, by inhibiting prostacyclin (PGI2) synthesis, may affect the tone of vascular smooth muscle. In addition to lipid peroxides, vascular endothelium may also interact with hydrogen peroxide (H2O2) derived from polymorphonuclear leukocytes (PMN). The PMN derived H2O2 stimulates PGI2 production by endothelial cells at sites of inflammation (Harlan and Callahan 1984). The integrity of vascular endothelium is obligatory for many vasoactive compounds to elicit relaxation (Furchgott and Zawadzki 1980). This endothelium dependent relaxation is abolished by Superoxide anion (O.— 2) (Rubanyi and Vanhoutte 1986). Little is known of the vascular activity of peroxides and therefore we have investigated the effect of several peroxides on the tone of isolated blood vessels with and without endothelium.
KeywordsMethylene Blue Guanylate Cyclase Vascular Reactivity Endothelium Dependent Relaxation Soluble Guanylate Cyclase
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