Oxidized low-density lipoprotein enhances myogenic tone in the rabbit posterior cerebral artery through the release of endothelin-1.
OBJECTIVE
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.
Xie
H
H
Totman Laboratory for Cerebrovascular Research, Department of Pharmacology, College of Medicine, University of Vermont, Burlington 05405-0068, USA.
Bevan
J A
JA
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001794:Blood Pressure / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D020769:Posterior Cerebral Artery / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects* / Q000378:metabolism
D000470:Alkaloids; D053119:Benzophenanthridines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010456:Peptides, Cyclic; D010617:Phenanthridines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D011189:Potassium Chloride; C016299:chelerythrine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine