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 PGF2 alpha 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 Ca(2+)-free medium. Indomethacin only inhibited the veratridine-induced potentiation of Ca2+ responses. Veratridine increased the level of PGF2 alpha 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.
Morikawa
M
M
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Satake
N
N
Shibata
S
S
Shibata
T
T
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D015237:Dinoprost / Q000502:physiology; D015232:Dinoprostone / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D014701:Veratridine / Q000494:pharmacology*
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D014701:Veratridine; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone