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, were compared on the isolated porcine coronary artery with intact and removed endothelium. All three forms of nicardipine inhibited the contractions induced by KCl (5-90 mM) in both vessel preparations. The potency (IC50) of the (+)-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 vessel 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 statistically 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. Quantitatively, the inhibition of contraction was stereoselective, the (+)-S enantiomer being the most potent, and was endothelium-independent.
Japelj
I
I
Department of Pharmacology and Experimental Toxicology, Medical Faculty, Ljubljana, Slovenia.
Budihna
M V
MV
Stanovnik
L
L
Krisch
I
I
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009529:Nicardipine / Q000737:chemistry / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D013237:Stereoisomerism; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D011189:Potassium Chloride; D009529:Nicardipine