Effects of the new long-acting dihydropyridine calcium antagonist pranidipine on the endothelium-dependent relaxation in isolated rat aorta in 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, CAS 99522-79-9) on the endothelium-dependent relaxation in the isolated aorta in vitro was examined in comparison with other calcium antagonists (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 contracted with prostaglandin F2 alpha. This endothelium-dependent relaxation recovered within a few minutes, although the mechanisms of this contraction after relaxation were not clear. The pretreatment with pranidipine for 20 min extended the duration of the endothelium-dependent relaxation, however, there was no potentiation in magnitude of the relaxation. This effect on the duration of endothelium-dependent relaxation was prominent in pranidipine, namely, other calcium antagonists tested 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 beneficial feature for therapeutic use of the compound.