Oxidized low-density lipoprotein enhances myogenic tone in the rabbit posterior cerebral artery through the release of endothelin-1

Background and Purpose-Cerebral arteries develop stretch-induced myogenic t one, which plays an important role in the regulation of blood flow to the b rain. Although the effect of oxidized LDL (Ox-LDL) on many aspects of the v ascular endothelial and smooth muscle cell function have been extensively i nvestigated, its influence on myogenic activity has not been studied. Methods-The effect of Ox-LDL on the myogenic tone that develops in the perf used rabbit posterior cerebral artery at intramural pressures between 40 an d 90 mm Hg was examined. Results-Ox-LDL (10 mu g/mL) significantly enhanced myogenic tone by 21.4+/- 6.1% to 28.5+/-1.8% at 60 to 90 mm Hg pressure (P<0.05) but had no influenc e on norepinephrine- (0.5 to 1 mu mol/L) and KCl (20 mmol/l)- induced const riction. Ox-LDL was effective whether the artery was exposed to it from the intraluminal or the extraluminal surface. Lysophosphatidylcholine (10 mu m ol/L), a lipid component of Ox-LDL, had an equivalent potentiating effect. Native LDL (100 mu g/mL) was inactive. The myogenic tone-potentiating effec t of Ox-LDL was abolished by endothelium removal but was not influenced by the NO synthase inhibitor N-G-nitro-L-nitro-arginine methyl eater (50 mu mo l/L). This effect was reversed by the endothelin-1 (ET-1) antagonist BQ-123 (1 mu mol/L). This concentration blocked 1 to 3 nmol/L ET-1-induced constr iction without altering constriction induced by 40 mmol/L KCl. The potentia ting effect was suppressed by the specific protein kinase C inhibitor chele rythrine (1 mu mol/L). Conclusions-Ox-LDL enhances myogenic tone through the release of ET-1 from the endothelium of the rabbit posterior cerebral artery.