Inhibition of endothelium-dependent arterial relaxation by oxidized phosphatidylcholine.
Formation of oxidized phosphatidylcholine (ox-PC), oxidatively fragmented phosphatidylcholine (PC) containing a short-chain and/or polar oxidative residue at the sn-2 position, in the process of LDL oxidation as well as its existence in atherosclerotic lesions has been demonstrated. To clarify the pathophysiological role of ox-PC in the vascular reactivity, we investigated the effects of various ox-PCs on the isometric tensions in rabbit thoracic aortas. Ox-PCs, which were produced upon oxidation of sn-2 polyunsaturated fatty acid (PUFA)-containing PCs, dose-dependently inhibited endothelium-dependent relaxation (EDR) evoked by acetylcholine or substance P. On the other hand, neither native PUFA-containing PCs nor an oxidative product of monounsaturated fatty acid-containing PC showed an inhibitory effect. None of ox-PCs affected endothelium-independent relaxation to nitroglycerin. The PC-headgroup fraction, but not the oxidized fatty acids fraction, was responsible for the inhibition of EDR by ox-PC. EDR was reduced by 2-(5-oxovaleroyl)-PC, one of the secondary oxidative products of PCs that contains a short chain aldehydic residue at the sn-2 position, but not by PC hydroperoxide, the primary oxidative product. Although the possibility could not be completely ruled out that lysophosphatidylcholine rather than ox-PC may be responsible for inhibitory effects on EDR, these results suggest a novel vascular activity of ox-PCs generated from sn-2 PUFA-containing PCs which may be implicated in the pathophysiology of vascular tone.
Rikitake
Y
Y
The First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan.
Hirata
K
K
Kawashima
S
S
Inoue
N
N
Akita
H
H
Kawai
Y
Y
Nakagawa
Y
Y
Yokoyama
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000503:physiopathology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005996:Nitroglycerin / Q000494:pharmacology; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D011336:Probability; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D010713:Phosphatidylcholines; D005996:Nitroglycerin; D000109:Acetylcholine