Impairment of acetylcholine relaxations by malondialdehyde, a marker of lipid peroxidation.
The effect of malondialdehyde (MDA), a lipid peroxidation marker, on the relaxations evoked by acetylcholine (ACh) was analyzed in tail arteries of Sprague-Dawley rats, which have MDA plasma levels of 0.43 +/- 0.10 microM. MDA (0.5-30 microM) produced an inhibition of ACh relaxations that persisted after repeated washing periods, and was independent of the incubation time. MDA did not modify the vasodilator responses to either exogenous nitric oxide (NO) or sodium nitroprusside, a NO donor. L-Arginine (the NO synthase substrate) did not prevent the impairment of relaxations to ACh caused by MDA. The association of N omega-nitro-L-arginine methyl ester (a NO synthase inhibitor) and MDA produced an additive inhibition of the ACh-induced relaxations. Superoxide dismutase (a superoxide anion scavenger) completely reversed the inhibitory effect of MDA. These results suggest: (1) MDA is not only a marker of lipid peroxidation but also an agent that can impair endothelium-dependent relaxations; (2) this impairment does not seem to be due to an interference with guanylate cyclase activation by NO or with NO synthase pathway; (3) the effect of MDA appears to be mediated by superoxide anion, and (4) MDA could propagate lipid peroxidation chain reactions in endothelial membranes, that could alter the function of muscarinic receptors.
Rodríguez-Martínez
M A
MA
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Martínez-Orgado
J
J
Salaices
M
M
Marín
J
J
D000109:Acetylcholine / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D008054:Lipid Peroxides / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D008054:Lipid Peroxides; D009599:Nitroprusside; D009569:Nitric Oxide; D008315:Malondialdehyde; D000109:Acetylcholine; D000111:Acetylcysteine