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(Hypertension. 2001;37:240.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Nifedipine Increases Endothelial Nitric Oxide Bioavailability by Antioxidative Mechanisms

Reinhard Berkels; Guido Egink; Tobias A. Marsen; Henning Bartels; Renate Roesen; Wolfgang Klaus

From the Institute of Pharmacology (R.B., H.B., R.R., W.K.) and Clinic IV of Internal Medicine (G.E., T.A.M.), University of Cologne, Cologne, Germany.

Correspondence to Dr Reinhard Berkels, Institut fuer Pharmakologie, Gleueler Str 24, 50931 Koeln, Germany. E-mail Reinhard.Berkels{at}medizin.uni-koeln.de

Short-term treatment of the endothelium with dihydropyridine calcium antagonists resulted in an increased release in NO that is not due to a modulation of L-type calcium channels, because macrovascular endothelial cells do not express this channel. We investigated whether long-term (48 hours) treatment of porcine endothelial cell cultures with the dihydropyridine calcium antagonist nifedipine resulted in a similar enhanced NO liberation. Regarding to the underlying mechanism, we examined whether (1) nifedipine changed the mRNA and protein levels of the constitutive endothelial NO synthase (NOS) in endothelial cell cultures or (2) nifedipine exerts an NO protective effect via its antioxidative properties, as revealed in a cell culture model and with native endothelium from porcine coronary arteries. Nifedipine induced a significant time- and concentration-dependent increase (132±47%, 1 µmol/L, 40 minutes’ incubation) in the basal NO liberation (oxyhemoglobin assay). This increased NO release was not due to elevated NOS (type III) mRNA (Northern blot analysis) and protein (Western blot analysis) levels. However, nifedipine (both short- and long-term treatment) significantly reduced the basal and glucose (20 and 30 mmol/L)-stimulated formation of reactive oxygen species (lucigenin assay) of endothelial cell cultures and native cells. We conclude that the calcium antagonist nifedipine enhances the bioavailability of endothelial NO without significantly altering the NOS (type III) mRNA and protein expression, possibly via an antioxidative protection. This increased NO availability may cause part of the vasodilation and might contribute to the antithrombotic, antiproliferative, and antiatherosclerotic effects of dihydropyridine calcium antagonists.

Key Words: antioxidants • calcium antagonists • endothelium • nitric oxide • nitric oxide synthase • protein • nifedipine

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