Cross-perfused canine atrial preparations were used to investigate the direct and indirect cardiac actions of
clonidine and
alinidine.
Intravenous injections of
clonidine (0.1-3 micrograms/kg) produced an initial brief pressor response and
bradycardia followed by
hypotension in the intact dog. Chronotropic and inotropic responses were absent in the isolated atrium perfused with the intact dog's blood. Intravenous
clonidine (10-300 micrograms) also induced negative chronotropic and inotropic effects in isolated atria. On the other hand,
alinidine, at doses which caused a depressor action and
bradycardia in the intact dog, consistently produced negative chronotropic and inotropic effects in the isolated atrium. Therefore, it was confirmed that a relatively small dose of
clonidine has a selective vascular action, while
alinidine has direct
cardiac depressant properties at all effective doses. Negative chronotropic and inotropic effects of peripheral vagal stimulation,
carbachol and
adenosine were not significantly modified by 100 or 300 micrograms doses of intraarterial
clonidine. On the other hand, the effects of vagal stimulation and
carbachol were significantly inhibited by 100 and 300 micrograms of
alinidine, without affecting
adenosine-induced cardiac actions. Therefore, it was demonstrated that
alinidine has anti-
muscarinic properties.