Abstract:
BACKGROUND AND PURPOSE:Cerebral arteries develop stretch-induced myogenic tone, which plays an important role in the regulation of blood flow to the brain. Although the effect of oxidized LDL (Ox-LDL) on many aspects of the vascular endothelial and smooth muscle cell function have been extensively investigated, its influence on myogenic activity has not been studied. METHODS:The effect of Ox-LDL on the myogenic tone that develops in the perfused rabbit posterior cerebral artery at intramural pressures between 40 and 90 mm Hg was examined. RESULTS:Ox-LDL (10 microg/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 influence on norepinephrine- (0.5 to 1 micromol/L) and KCl (20 mmol/L)-induced constriction. Ox-LDL was effective whether the artery was exposed to it from the intraluminal or the extraluminal surface. Lysophosphatidylcholine (10 micromol/L), a lipid component of Ox-LDL, had an equivalent potentiating effect. Native LDL (100 microg/mL) was inactive. The myogenic tone-potentiating effect of Ox-LDL was abolished by endothelium removal but was not influenced by the NO synthase inhibitor N(G)-nitro-L-nitro-arginine methyl ester (50 micromol/L). This effect was reversed by the endothelin-1 (ET-1) antagonist BQ-123 (1 micromol/L). This concentration blocked 1 to 3 nmol/L ET-1-induced constriction without altering constriction induced by 40 mmol/L KCl. The potentiating effect was suppressed by the specific protein kinase C inhibitor chelerythrine (1 micromol/L). CONCLUSIONS:Ox-LDL enhances myogenic tone through the release of ET-1 from the endothelium of the rabbit posterior cerebral artery.
journal_name
Strokejournal_title
Strokeauthors
Xie H,Bevan JAdoi
10.1161/01.str.30.11.2423subject
Has Abstractpub_date
1999-11-01 00:00:00pages
2423-29; discussion 2429-30issue
11eissn
0039-2499issn
1524-4628journal_volume
30pub_type
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