4-Hydroxynonenal, a Lipid Peroxidation Product, Induces Relaxation of Human Cerebral Arteries

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Abstract
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 F2α (PFG2α; 10−7-3 × 10−6 M), 100% relaxation was obtained with 3 × 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 × 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 ≈50%, but relaxation could not be abolished. When the endothelium was removed, 4-HNE did not promote relaxation after PGF2α stimulation. The possible roles of different intracellular signaling systems in the vascular effect of 4-HNE are discussed.