Oxidized low-density lipoprotein antagonizes the activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor but does not interfere with its biosynthesis.
Oxidized low-density lipoprotein (LDLox) is a molecule with strong atherogenic properties. In a concentration dependent fashion, LDLox antagonized the activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor (EDRF), which was produced in vitro by incubation of a partially purified EDRF-forming enzyme in the presence of L-arginine, Ca2+ and NADPH. The inhibitory effect of LDLox was potentiated by preincubation of the soluble guanylate cyclase with LDLox, but not when the EDRF-forming enzyme was pretreated with LDLox. As LDLox did not diminish the calmodulin-dependent conversion of L-arginine into L-citrulline by the EDRF-forming enzyme it would appear that EDRF-biosynthesis was not affected by LDLox. It is suggested that the impaired relaxant response of atherosclerotic blood vessels to endothelium-dependent vasodilators was not due to a reduced formation of EDRF but due to a diminished responsiveness of soluble guanylate cyclase.
Schmidt
K
K
Institut für Pharmakodynamik und Toxikologie, Universität Graz, Austria.
Graier
W F
WF
Kostner
G M
GM
Mayer
B
B
Böhme
E
E
Kukovetz
W R
WR
D000818:Animals; D004789:Enzyme Activation; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010084:Oxidation-Reduction; D012995:Solubility; D013552:Swine
D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D006162:Guanylate Cyclase