4-Hydroxynonenal, a lipid peroxidation product, induces relaxation of human cerebral arteries.
The relaxant effect of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, on human cerebral arteries was studied. Addition of 4-HNE to artery rings promoted no contraction, and after stimulation with prostaglandin F2 alpha (PFG2 alpha; 10(-7)-3 x 10(-6) M), 100% relaxation was obtained with 3 x 10(-5) M 4-HNE. Inhibition of nitric oxide formation with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; (10(-4) M), as well as prostaglandin synthesis with indomethacin (3 x 10(-6) M), partially prevented 4-HNE-induced relaxation, but each of these substances separately failed to inhibit complete relaxation. Addition of both inhibitors together reduced 4-HNE-induced relaxation to approximately 50%, but relaxation could not be abolished. When the endothelium was removed, 4-HNE did not promote relaxation after PGF2 alpha stimulation. The possible roles of different intracellular signaling systems in the vascular effect of 4-HNE are discussed.
Department of Physiology, School of Medicine and Dentistry, University of Valencia, Spain.
M C
MC
Martínez
F
F
Bosch-Morell
A
A
Raya
J
J
Romá
M
M
Aldasoro
J
J
Vila
S
S
Lluch
F J
FJ
Romero
D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002102:Cadaver; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009994:Osmolar Concentration; D014664:Vasodilation
D000447:Aldehydes; D008054:Lipid Peroxides; D009569:Nitric Oxide; D001120:Arginine; D015237:Dinoprost; C027576:4-hydroxy-2-nonenal; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin