EFFECTS OF THE NEW LONG-ACTING DIHYDROPYRIDINE CALCIUM-ANTAGONIST PRANIDIPINE ON THE ENDOTHELIUM-DEPENDENT RELAXATION IN ISOLATED RAT AORTAIN-VITRO

The action of methyl 3-phenyl-2(E)-propenyl 1,4-dihydro-2,6-dimethyl- 4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (pranidipine, OPC-13340, C AS 99522-79-9) on the endothelium-dependent relaxation in the isolated aorta in vitro was examined in comparison with other calcium antagoni sts (nifedipine, nitrendipine, nicardipine, diltiazem and verapamil). In the isolated aortic preparation of Wistar rats, acetylcholine (10(- 5) mol/l), ATP (10(-5) mol/l or histamine (10(-5)-10(-4) mol/l) caused endothelium-dependent relaxation when the strips were previously cont racted with prostaglandin F2alpha. This endothelium-dependent relaxati on recovered within a few minutes, although the mechanisms of this con traction after relaxation were not clear. The pretreatment with pranid ipine for 20 min extended the duration of the endothelium-dependent re laxation, however, there was no potentiation in magnitude of the relax ation. This effect on the duration of endothelium-dependent relaxation was prominent in pranidipine, namely, other calcium antagonists teste d had not this action at clinical concentrations. This phenomenon was also observed when the strips were pre-contracted with norepinephrine. This action of pranidipine might be some beneficical feature for ther apeutic use of the compound.