Zatebradine attenuates cyclic AMP-related positive chronotropic but not inotropic responses in isolated, perfused right atria of the dog

Clinical and Experimental Pharmacology & Physiology
S SawakiS Chiba

Abstract

1. Inhibition of I(f) or ICa by zatebradine has been reported in mammalian SA nodal cells. We thus investigated whether zatebradine differentially attenuates the positive chronotropic and inotropic responses to norepinephrine, isoproterenol, NKH 477 (an adenylyl cyclase activator), 3-isobutyl-1-methylxanthine (IBMX) and Bay k 8644 (a calcium channel agonist) in the isolated, blood-perfused dog atrium. 2. When zatebradine (0.03-1 mumol) decreased sinus rate from 104 +/- 4.5 to 73 +/- 4.9 beats/min dose-dependently, it selectively attenuated the positive chronotropic but not inotropic responses to norepinephrine in a dose-related manner. Zatebradine decreased the norepinephrine-induced tachycardia (by approximately 80% from the control) more effectively than the spontaneous sinus rate (by approximately 30% from the control). 3. Zatebradine similarly attenuated the positive chronotropic but not inotropic responses to isoproterenol, NKH 477 and IBMX. Fifty per cent inhibition doses of zatebradine (0.10-0.18 mumol) for the chronotropic responses to each substance were not significantly different. 4. On the other hand, zatebradine attenuated neither positive chronotropic nor inotropic responses to Bay k 8644. 5. We therefore suggest ...Continue Reading

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Citations

Feb 10, 2000·European Journal of Pharmacology·H NaitoK Hashimoto
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Robin A FelderPedro A Jose
May 2, 2003·Expert Opinion on Investigational Drugs·Masao Endoh
Nov 11, 2008·Physiology & Behavior·Eugene NalivaikoAndrea Sgoifo
May 10, 2002·Journal of Cardiovascular Pharmacology and Therapeutics·Luyi SenBramah N Singh
Aug 29, 2002·Journal of Cardiovascular Pharmacology·Masao Endoh
Apr 29, 1998·Journal of Cardiovascular Pharmacology·M SakamotoE L Yellin

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