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.