4-HYDROXYNONENAL, A LIPID-PEROXIDATION PRODUCT, INDUCES RELAXATION OFHUMAN 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 pros taglandin F-2 alpha (PFG(2 alpha); 10(-7)-3 x 10(-6) M), 100% relaxati on was obtained with 3 x 10(-5) M 4-HNE. Inhibition of nitric oxide fo rmation with N-G-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 t hese substances separately failed to inhibit complete relaxation. Addi tion of both inhibitors together reduced 4-HNE-induced relaxation to a pproximate to 50%, but relaxation could not be abolished. When the end othelium was removed, 4-HNE did not promote relaxation after PGF(2 alp ha) stimulation. The possible roles of different intracellular signali ng systems in the vascular effect of 4-HNE are discussed.