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Nifedipine increases endothelial nitric oxide bioavailability by antioxidative mechanisms
R Berkels1, G Egink, T A Marsen
1Institute of Pharmacology, University of Cologne, Cologne, Germany. Reinhard.Berkels@medizin.uni-koeln.de
Hypertension (Dallas, Tex. : 1979)
|March 7, 2001
Summary
Nifedipine, a calcium antagonist, boosts nitric oxide (NO) release from endothelial cells. This effect is linked to its antioxidant properties, not changes in NO synthase levels, suggesting a role in vasodilation and antiatherosclerotic effects.
Area of Science:
- Cardiovascular Pharmacology
- Endothelial Biology
- Nitric Oxide Signaling
Background:
- Dihydropyridine calcium antagonists increase nitric oxide (NO) release, but the mechanism is unclear, especially in endothelial cells lacking L-type calcium channels.
- Previous studies showed short-term nifedipine treatment enhanced NO release, prompting investigation into long-term effects and mechanisms.
Purpose of the Study:
- To investigate if long-term nifedipine treatment enhances NO liberation in porcine endothelial cells.
- To determine if nifedipine affects endothelial nitric oxide synthase (NOS) mRNA and protein levels.
- To examine if nifedipine's antioxidative properties contribute to NO enhancement.
Main Methods:
- Porcine endothelial cell cultures were treated with nifedipine for varying durations and concentrations.
- Nitric oxide (NO) liberation was measured using the oxyhemoglobin assay.
- Endothelial nitric oxide synthase (NOS) mRNA and protein levels were assessed via Northern and Western blot analyses, respectively.
- Reactive oxygen species (ROS) formation was quantified using the lucigenin assay in both cell cultures and native endothelium.
Main Results:
- Nifedipine induced a significant, time- and concentration-dependent increase in basal NO liberation.
- This enhanced NO release was not associated with increased NOS (type III) mRNA or protein levels.
- Nifedipine significantly reduced basal and glucose-stimulated reactive oxygen species (ROS) formation in endothelial cells and native endothelium.
Conclusions:
- Nifedipine enhances endothelial NO bioavailability, likely through an antioxidative mechanism rather than altering NOS expression.
- The increased NO availability may contribute to the vasodilatory, antithrombotic, antiproliferative, and antiatherosclerotic effects of dihydropyridine calcium antagonists.