Release of nitrogen oxides from cultured bovine aortic endothelial cells is not impaired by calcium channel antagonists.
BACKGROUND
The endothelium-derived relaxing factor has been shown to be nitric oxide or a related nitroso compound, synthesized by the enzyme nitric oxide synthetase, which oxidizes the guanidono nitrogens of arginine. This enzyme is activated by increases in cytosolic calcium. The effect of the clinically used calcium channel antagonists on this process is controversial. The present study was performed to determine whether calcium channel blockade with these pharmacologic agents would alter the activity of nitric acid synthetase in intact endothelial cells.


RESULTS
A specific and sensitive chemiluminescence assay was used to measure the release of nitrogen oxides (nitric oxide and one-electron oxidation products of nitric oxide) from bovine aortic endothelial cells grown in culture. Under basal conditions, the release of nitrogen oxides was about 0.2 nmol/100 micrograms protein/hr. Bradykinin doubled this response. Removal of extracellular calcium abolished basal and bradykinin-stimulated release of nitrogen oxides. Neither diltiazem, verapamil, nor nifedipine in concentrations that are encountered clinically altered the release of nitrogen oxides.


CONCLUSIONS
These experiments show that although the production of nitrogen oxides is dependent on extracellular calcium, the clinically used calcium channel antagonists do not inhibit the release of the endothelium-derived relaxing factor.
Mügge
A
A
Department of Internal Medicine, University of Iowa Hospital and Clinics, Iowa City.
Peterson
T
T
Harrison
D G
DG
D000594:Amino Acid Oxidoreductases / Q000187:drug effects*; D000818:Animals; D001011:Aorta / Q000166:cytology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009589:Nitrogen Oxides / Q000378:metabolism*
D002121:Calcium Channel Blockers; D009589:Nitrogen Oxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases