Positive Inotropic Action of Veratridine in Rat Atria: Possible Involvement of Prostanoids

Veratridine caused a positive inotropic action in the electrically driven left atria of rats. Quinacrine (a phospholipase A₂ inhibitor), indomethacin (a cyclooxygenase inhibitor) and aspirin (a cyclooxygenase inhibitor), but not nordihydroguaiaretic acid (a lipoxygenase inhibitor), inhibited the response to veratridine. Verapamil and nifedipine also inhibited the response to veratridine. The positive inotropic effect of arachidonic acid was abolished by aspirin and indomethacin. However, the positive inotropic effect of PGF_2α was not affected by indomethacin, quinacrine or aspirin. PGE₂, but not STA₂ and PGI₂, also caused the positive inotropic effect. However, the negative inotropic effect was observed in the presence of PGE₁ and PGD₂. Veratridine shifted the concentration-response curve of Ca2+ to the left in a Ca2+-free medium. Indomethacin only inhibited the veratridine-induced potentiation of Ca2+ responses. Veratridine increased the level of PGF_2α in the left atria and this action was completely inhibited by indomethacin, aspirin and quinacrine. Veratridine also increased the level of PGE₂. These results imply that the positive inotropic action of veratridine is partly due to stimulation of the release of arachidonic acid leading to the increase in prostaglandins in rat atria.