(Circulation. 1995;92:1582-1589.)
© 1995 American Heart Association, Inc.
Articles |
Impairment of Endothelium-Dependent Dilation in Rabbit Renal Arteries by Oxidized Lipoprotein(a)
Role of Oxygen-Derived Radicals
From the Department of Medicine, Division of Nephrology, University Hospital of Würzburg and the Department of Medicine, Division of Nephrology, University Hospital of Freiburg (J.B., P.S.),Germany.
Correspondence to Dr J. Galle, Dept of Medicine, Division of Nephrology, University Hospital Würzburg, Joseph-Schneider-Str 2, D-97080 Würzburg, Germany.
Background Hyperlipoproteinemia is associated with impairment of nitric oxide (NO)–mediated, endothelium-dependent dilation in renal arteries. In the present study, we assessed and compared the effects of human lipoprotein(a) and LDL on endothelium-dependent and -independent dilation in vitro.
Methods and Results Dilator responses were detected in isolated, saline-perfused, preconstricted arterial segments by a photoelectric device. Acetylcholine-induced, endothelium-dependent dilator responses of rabbit renal arteries were not significantly attenuated after 150 minutes of incubation with native lipoprotein(a) (30 and 100 µg/mL). However, exposure to in vitro oxidized lipoprotein(a) (150 minutes, 30 and 100 µg/mL) suppressed acetylcholine-induced dilator responses in a dose-dependent manner. At similar concentrations, native and oxidized LDL had no effect. Endothelium-independent dilations induced by the NO-donor sodium nitroprusside were also impaired by oxidized lipoprotein(a), whereas forskolin-induced dilator responses were unaffected, indicating that smooth muscle dilator capacity was not impaired. Attenuation of dilator responses by oxidized lipoprotein(a) was potentiated in the presence of superoxide dismutase (SOD). The SOD effect was completely blunted by coincubation with catalase (100 U/mL) or deferoxamine. In the absence of SOD, catalase or deferoxamine had no effect on dilator responses. Using a chemiluminescence assay, we could detect increased O2- production by arteries pretreated with oxidized lipoprotein(a), which suggested that enhanced NO inactivation by O2- could be the underlying mechanism for impairment of endothelium-dependent dilations.
Conclusions These data indicate that oxidized lipoprotein(a) impairs endothelium-dependent dilation and is more potent than oxidized LDL in this effect. The mechanism of the impairment may involve formation of O2- and inactivation of NO.
Key Words: nitric oxide • hypercholesterolemia • hypertension • anions
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