Enhancement of myocardial reactive hyperemia and adenosine-induced coronary vasodilation by dilazep, a new adenosine potentiator.

The effect of N,N'-bis[3'-(3",4",5"-trimethoxybenzoyloxy)-propyl]hexahydro-1, 4-diazepine (dilazep) on myocardial reactive hyperemia and coronary vasodilatory potency of adenosine was studied in the anesthetized open-chest dog. Dilazep injected i.v. was detected in the pericardial effusate, suggesting that the drug could enter the interstitial space of the heart. A threshold dose of dilazep increased vasodilatory action of exogenous adenosine. The dose of dilazep enhanced compensation for flow debt during myocardial reactive hyperemia caused by 5-, 10-, 15-, 20- and 30-s coronary occlusions, respectively, whereas peak flow rate was increased in response to only 5- and 10-s occlusions by dilazep, respectively. The results obtained suggest that dilazep potentiates the effect of endogenous adenosine which is released during ischemia and also suggest that adenosine plays important role in myocardial reactive hyperemia.