The effects of a newly synthetic alpha- and beta-
adrenoceptor blocking agent,
YM-09538, on SA nodal pacemaker activity and contractility of atria and intact dogs were studied using isolated and blood-perfused canine atrial muscle preparations supported by a donor dog.
Intravenous administration of
YM-09538 (10-100 micrograms/Kg) caused
hypotension without
tachycardia, but was accompanied with
bradycardia in anesthetized dogs. In these cases, the SA nodal pacemaker activity and atrial contractility in isolated atria was influenced little. This indicates that the concentration of YM-00538 that induces
hypotension has no direct cardiac effects. Direct administration of
YM-09538 to isolated atria caused dose-dependent negative chronotropic and inotropic effects, and the potency was 3-30 times less than that of
propranolol. In electrically paced preparations, a large dose of
YM-09538 produced a uniform depression of the developed tension at all frequencies examined (2-3 Hz). On the other hand,
verapamil caused a greater suppression of developed tension at higher frequencies, indicating that the mode of action of
YM-09538 is different from that of
verapamil.