Jpn. J. Pharmacol. 78 (4), 493-499 (1998)


Effects of Low Temperature on the Chronotropic and Inotropic Responses to Zatebradine, E-4031 and Verapamil in Isolated Perfused Dog Atria

Miho Kasama, Yasuyuki Furukawa (*), Takeshi Oguchi, Yuji Hoyano and Shigetoshi Chiba


Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
(*) To whom correspondence should be addressed.

Abstract: We investigated the effects of hypothermia (25 C) on the chronotropic and inotropic effects of zatebradine (a blocker of hyperpolarization-activated inward current, If), E-4031 (a blocker of the rapid type of the delayed rectifier K+ current, IKr) and verapamil, and on the positive cardiac responses to isoproterenol after treatment with zatebradine and E-4031 in isolated, blood-perfused dog atria. Hypothermia shifted the dose-response curves to the right for the negative chronotropic and inotropic effects of verapamil and for the negative chronotropic and positive inotropic effects of zatebradine, but not for the negative chronotropic and positive inotropic effects of E-4031. Hypothermia attenuated the positive chronotropic response to isoproterenol or Bay k 8644 (an L type Ca2+ channel agonist) and was attenuated more than the inotropic one. Zatebradine selectively inhibited the positive chronotropic response to isoproterenol at a normal temperature, but in hypothermia, it inhibited neither the chronotropic nor inotropic responses. E-4031 did not affect the positive responses to isoproterenol. These results suggest that verapamil and zatebradine but not E-4031 influence the atrial rate and contractile force much less in hypothermia than in normothermia and that the If and inward Ca2+ current are sensitive to hypothermia in the heart.

Keywords: Zatebradine, E-4031, Verapamil, Hypothermia, Dog heart


Copyrightę The Japanese Pharmacological Society 1998

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