Gewählte Publikation:
Schmidt, K; Graier, WF; Kostner, GM; Mayer, B; Bohme, E; Kukovetz, WR.
Stimulation of Soluble Guanylate-Cyclase by Endothelium-Derived Relaxing Factor Is Antagonized by Oxidized Low-Density-Lipoprotein
J CARDIOVASC PHARMACOL 1991 17: S83-S88.
Doi: 10.1097/00005344-199117003-00015
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- Co-Autor*innen der Med Uni Graz
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Graier Wolfgang
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Kostner Gerhard
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- Abstract:
- Atherosclerosis is associated with a diminished dilatory response of blood vessels to endothelium-derived relaxing factor (EDRF). To clarify whether this impaired response may be due to a reduced biosynthesis of EDRF or a diminished responsiveness of the smooth muscle guanylate cyclase to EDRF, we investigated the effects of oxidized low-density lipoprotein (LDLox), a lipoprotein with atherogenic properties, on the activation of purified soluble guanylate cyclase by EDRF, as well as on the activity of the partially purified EDRF-forming enzyme. In the presence of LDLox, the effects of EDRF and other nitrocompounds on soluble guanylate cyclase were dose-dependently diminished, whereas no effect of LDLox on basal guanylate cyclase activity was observed. The inhibitory effect could be potentiated by preincubation of the enzyme with LDLox, indicating a direct interaction between the lipoprotein and guanylate cyclase. In contrast to its inhibitory effect on guanylate cyclase, LDLox did not affect the activity of the EDRF-forming enzyme. These data indicate that the impaired response of atherosclerotic blood vessels may be due to a diminished responsiveness of the smooth muscle guanylate cyclase rather than a reduced biosynthesis of EDRF.
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Endothelium-Derived Relaxing Factor (EDRF)
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EDRF-Forming Enzyme
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Soluble Guanylate Cyclase
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Oxidized Low-Density Lipoprotein