Activation of soluble guanylate cyclase by nitrovasodilators is inhibited by oxidized low-density lipoprotein.
In the presence of oxidized low-density lipoprotein the stimulatory effects of nitric oxide, sodium nitroprusside and S-nitrosoglutathione on soluble guanylate cyclase partially purified from bovine platelets were diminished in a concentration-dependent manner with IC50 values around 100 micrograms total cholesterol/ml. This inhibitory effect was potentiated about 10-fold when the enzyme was pre-incubated with the lipoprotein for 10 minutes at 37 degrees C which indicates a direct interaction of the lipoprotein with the guanylate cyclase. As oxidized low-density lipoprotein is present in the wall of atherosclerotic arteries, we suggest that the impaired response of atherosclerotic blood vessels to vasodilators may be due to a diminished activation of smooth muscle guanylate cyclase.
Schmidt
K
K
Institut für Pharmakodynamik und Toxikologie, Karl-Franzens-Universität Graz, Austria.
Graier
W F
WF
Kostner
G M
GM
Mayer
B
B
Kukovetz
W R
WR
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D002417:Cattle; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000097:blood* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood* / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D026422:S-Nitrosoglutathione; D014665:Vasodilator Agents / Q000494:pharmacology*
D008074:Lipoproteins; D009603:Nitroso Compounds; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D006162:Guanylate Cyclase; D005978:Glutathione