Stereoselective inhibition of thromboxane‐induced coronary vasoconstriction by 1,4‐dihydropyridine calcium channel antagonists
- 1 January 1990
- Vol. 2 (4) , 233-240
- https://doi.org/10.1002/chir.530020408
Abstract
The biological activity of the (+)‐S‐ and (−)‐R‐enantiomers of niguldipine, of the (−)‐S‐ and (+)‐R‐enantiomers of felodipine and nitrendipine, and of rac‐nisoldipine and rac‐nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)‐mimetic U‐46619 in guinea pig Langendorff hearts, displacement of (+)‐[3H]isradipine from calcium channel binding sites of guinea pig skeletal muscle T‐tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross‐contamination was 2‐induced coronary vasoconstriction in guinea pig Langendorff hearts can be readily explained by a transmembrane influx of extracellular Ca2+ susceptible to stereoselective blockade by 1,4‐dihydropyridine calcium channel antagonists.Keywords
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