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(Stroke. 1999;30:2423-2430.)
© 1999 American Heart Association, Inc.

Original Contributions

Oxidized Low-Density Lipoprotein Enhances Myogenic Tone in the Rabbit Posterior Cerebral Artery Through the Release of Endothelin-1

Hui Xie, MD, PhD John A. Bevan, MD

From the Totman Laboratory for Cerebrovascular Research, Department of Pharmacology, College of Medicine, University of Vermont, Burlington.

Correspondence to: Dr John A. Bevan, Totman Laboratory for Cerebrovascular Research, Department of Pharmacology, Given Bldg, College of Medicine, University of Vermont, Burlington, VT 05405-0068.

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 µg/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 µmol/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 µmol/L), a lipid component of Ox-LDL, had an equivalent potentiating effect. Native LDL (100 µg/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 µmol/L). This effect was reversed by the endothelin-1 (ET-1) antagonist BQ-123 (1 µmol/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 µmol/L).

Conclusions—Ox-LDL enhances myogenic tone through the release of ET-1 from the endothelium of the rabbit posterior cerebral artery.

Editorial Comment

William G. Mayhan, PhD, Guest Editor

Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska

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