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Učinki racemata in posameznih enantiomerov nikardipina na izolirano prašičjo koronarno arterijo z ohranjenim in odstranjenim endotelijem : magistrsko delo
Japelj, Irena
Introduction: Chiral calcium channel antagonists of 1,4 dihydropyridine group (DHP), nicardipine among them, are synthesized and used as racemic mixtures. Both enantiomers of DHP differ ...quantitatively and some also qualitatively. Theprimary and well recognised mechanism of calcium channel antagonists actionis at voltage-gated calcium channels on the vascular smooth muscle cells. The role of the vascular endothelium in the action of calcium channel antagonists in the isolated blood vessels is not totally elucidated. Aim: In the present study I investigated qualitative and quantitative effects of all three forms of nicardipine (S-(+), R-(-) enantiomer and racemic nicardipine) on the isolated porcine coronary artery with intact and mechanically removed endothelium with the aim to determine the role of stereoisomerism (enantiomerism) and the presence of the intact endothelium in the action of nicardipine. Materials and methods: Pig hearts (250-420 g, n=68) were transported from local slaughterhouse in Krebs-Henseleit solution with ice. Left anterior descending coronary artery (LAD) was isolated and three consecutive rings (4-6 mm wide), 5 mm from the beginning of the LAD artery, were cut and transferred into Krebs-Henseleit solution areated with 95 % + 5 %COZ at 37 *C. In some experiments endothelium was intact and in others removed by a thin steel needle. The presence of the endothelium was verified by substance P (10 nM) on the rings precontracted with KCl (27 mM). The contractions were measured isometrically, initial tension was 50 mN. To inducecontrol contraction, KCl was added in a žeries of concentrations (5-90 mM). Either one enantiomer or racemic nicardipine in a single cor,centration (10 pM0.1 mM) was added 30 minutes before the second series of KC1 (5-90 mM) additions. (Abstract truncated at 2000 characters).
Type of material - master's thesis
Publication and manufacture - Ljubljana : [I.Japelj], 1998
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