Stereoselective and endothelium-independent action of nicardipine on the isolated porcine coronary artery

The qualitative and quantitative effects of the (+)-S and (-)-R enantiomers and of the racemic mixture of the Ca2+ channel antagonist, nicardipine, we re compared on the isolated porcine coronary artery with intact and removed endothelium. All three forms of nicardipine inhibited the contractions ind uced by KCl (5-90 mM) in both vessel preparations. The potency (IC50) of th e (+)-S and (-)-R enantiomers and of the racemic mixture was 6.6, 31.8 and 10.9 nM in the vessel with endothelium and 6.4, 41.9 and 9.8 nM in the vess el without endothelium. The parameters of the concentration-response curves for each form of nicardipine at a submaximal KCl (60 mM) concentration and the potency ratios between the two enantiomers ((+)-S/(-)-R) were not stat istically significantly different (P > 0.05) in the two vessel preparations . In conclusion, qualitatively, all three forms of nicardipine showed only Ca2+ channel antagonistic effects in both vessel preparations. Quantitative ly, the inhibition of contraction was stereoselective, the (+)-S enantiomer being the most potent, and was endothelium-independent. (C) 1999 Elsevier Science B.V. All rights reserved.