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ZATEBRADINE ATTENUATES CYCLIC AMP‐RELATED POSITIVE CHRONOTROPIC BUT NOT INOTROPIC RESPONSES IN ISOLATED, PERFUSED RIGHT ATRIA OF THE DOG
Author(s) -
Sawaki Shoji,
Furukawa Yasuyuki,
Inoue Yasurou,
Oguchi Takeshi,
Chiba Shigetoshi
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb01914.x
Subject(s) - chronotropic , inotrope , medicine , endocrinology , ibmx , norepinephrine , heart rate , receptor , blood pressure , forskolin , dopamine
SUMMARY 1. Inhibition of I f or I ca 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 μmol) 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 μmol) 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 that zatebradine selectively attenuates the positive chronotropic but not inotropic responses to cyclic AMP‐related substances due to inhibition of I f but not I ca in the dog heart.