Melatonin inhibits vasospastic action of oxidized low-density lipoprotein in human umbilical arteries

We evaluated the antioxidant property of melatonin in countering the vasosp astic effect of oxidized low-density lipoprotein (ox-LDL), which has been r eported to be the most important risk factor for atherosclerosis and also m ay be linked to preeclampsia. Helical sections of umbilical arteries were o btained from human placentas at elective cesarean deliveries between 37 and 39 weeks of gestation. Changes in maximal tension induced by potassium chl oride were measured in arterial sections with intact endothelium. ox-LDL (2 00 or 300 mu g protein/mL) increased vascular tension by 15.6 +/- 2.3 or 31 .9 +/- 4.0%, respectively. In contrast, native LDL only slightly increased vascular tension (2.7 +/- 1.0% for 200 mu g protein/mL and 6.0 +/- 1.7% for 300 mu g protein/mL). Pretreatment with L-N-G-monomethyl-arginine (2 x 10( -4) M) significantly reduced the vasospastic effect of ox-LDL, as did pretr eatment with mannitol (30 mM). Melatonin (10 mu M) significantly reduced th e vasospastic effect of ox-LDL. These findings suggest that ox-LDL potentia tes vascular tension in the human umbilical artery, possibly by suppressing endothelial synthesis of nitric oxide. Melatonin significantly suppressed the vasospastic effect of ox-LDL, probably because it scavenges hydroxyl ra dical arising from ox-LDL.