Potentiation by acetylcholine of the effects of a calcium channel activator, Bay k 8644, on dog atria in situ.

The effects of Bay k 8644 were studied in the canine in situ heart under vagal influence and out of this influence on sinus rate and sinus recovery time, conduction time and effective refractory period (ERP) in the atrioventricular (AV) node and ERP of the atrial muscle. Bay k 8644, intravenously infused at the 2 micrograms X kg-1 X min-1 rate for 30 min, enhanced the inhibition of the atrial specialized tissue as well as the shortening of the atrial muscle ERP during vagal activity, elicited by the injection of dextromoramide into the cisterna magna. It did not develop any atrial action in the absence of vagal activity, suppressed by atropine. The reflex increase of vagal tone, in response to a small increase in blood pressure produced by Bay k 8644, is not the only cause of the phenomena observed in the former case. The observations can be explained primarily in terms of an interaction between Bay k 8644 and acetylcholine (ACh):ACh intraaortically injected near the coronary ostia, in a dose just sufficient to slow down sinus rate before Bay k 8644, reduced the rate by 50% at the end of a 60 min infusion of Bay k 8644 and the ACh threshold dose necessary to elicit a short third degree AV block before Bay k 8644 was reduced by 50% at the end of a 30 min infusion of Bay k 8644. Therefore, ACh appeared to be capable of enhancing the effects of a calcium channel activator as well as the effects of hypercalcaemia, as earlier reported.