High-density lipoprotein antagonizes the inhibitory effects of oxidized low-density lipoprotein and lysolecithin on soluble guanylyl cyclase.
Oxidatively modified LDL (LDLox) reduces the response of soluble guanylyl cyclase to nitrovasodilators. We now demonstrate that this desensitization can be antagonized by HDL. Similar to its protective effect against LDLox, HDL also inhibited the lysolecithin-induced desensitization of soluble guanylyl cyclase. Since the lysolecithin content of LDLox correlated with the amount of lysolecithin necessary to diminish stimulation of soluble guanylyl cyclase, our data support the hypothesis that lysolecithin may be responsible for the inhibitory effect of LDLox on smooth muscle relaxation and provide evidence that the antagonistic effect of HDL against desensitization of soluble guanylyl cyclase by atherogenic compounds could be responsible for the protective role of HDL in atherosclerosis.
Institut für Pharmakodynamik und Toxikologie, Karl-Franzens-Universität Graz, Austria.
K
K
Schmidt
P
P
Klatt
W F
WF
Graier
G M
GM
Kostner
W R
WR
Kukovetz
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D002417:Cattle; D003600:Cytosol / Q000201:enzymology; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000037:antagonists & inhibitors / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D053440:Lipoproteins, HDL3; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism / Q000494:pharmacology; D026422:S-Nitrosoglutathione
D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008244:Lysophosphatidylcholines; D009603:Nitroso Compounds; D009599:Nitroprusside; D016718:Arachidonic Acid; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D010741:Phospholipases A; D006162:Guanylate Cyclase; D005978:Glutathione