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  • Title: Relaxant effects of pinacidil, nicorandil, hydralazine and nifedipine as studied in the porcine coronary artery and guinea-pig taenia coli.
    Author: Matsui K, Ogawa Y, Imai S.
    Journal: Arch Int Pharmacodyn Ther; 1986 Sep; 283(1):124-33. PubMed ID: 2948465.
    Abstract:
    Effects of pinacidil, a newly synthesized vasodilator, on contractures induced in the porcine coronary artery and the guinea-pig taenia coli were investigated in comparison with those of nicorandil, hydralazine and nifedipine. These four substances produced a dose-dependent relaxation of K+-induced contracture in the coronary artery, and the order of relaxant activity was nifedipine greater than pinacidil greater than hydralazine divided by nicorandil (IC50: 1.62 X 10(-8), 1.98 X 10(-4), 1.70 X 10(-3), 2.35 X 10(-3) M, respectively). Hydralazine inhibited the contraction induced by caffeine in a Ca2+-free (EGTA) high potassium medium in a concentration-dependent manner (IC50: 8.43 X 10(-3) M). Pinacidil and nicorandil produced a partial inhibition of this contraction (45.2, 22.3% inhibition at 10(-2) M, respectively), while nifedipine was ineffective. In the isolated guinea-pig taenia coli, these compounds caused a concentration-dependent relaxation. The relaxant action by pinacidil and nicorandil was more potent in spontaneously contracting preparation or in preparations contracted by 30 mM [K+]0 than in preparations contracted by 100 mM [K+]0, while the reverse was true with nifedipine. Hydralazine was effective at similar concentrations on these three types of contraction. From these findings it was inferred that the smooth muscle relaxing-action of pinacidil and nicorandil was ascribable to the inhibitory action on the spontaneous spike activities of the surface membrane. Inhibition of the mobilization of calcium from intracellular store sites may play some role.
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