Abstract
The effects on the coronary circulation of RA233, a recently developed analog of dipyridamole, were investigated in the acutely transplanted dog heart and compared with those of dipyridamole and adenosine. Close arterial infusions of RA233 increased coronary blood flow within 30 seconds and this returned to control values within 15 minutes of stopping the infusion. In contrast, dipyridarnole increased coronary blood flow only after two minutes of infusion, and after stopping the infusion had a longer residual effect which lasted for 60 minutes. The dose-response curves for RA233 and dipyridamole were parallel and showed that RA233 was only from 1/20 to 1/30 as potent as dipyridamole. Equipotent low dose infusions of both RA233 and dipyridamole potentiated to a similar degree the coronary vasodilator actions of adenosine, shifting the dose-response curve for adenosine to the left in a parallel manner. Low dose infusions of aminophylline alone uniformly produced small reductions in coronary blood flow (16 ±4%) and increased coronary vascular resistance and also blocked the coronary vasodilator actions of RA233, dipyridamole and adenosine. RA233 responses were significantly less inhibited by aminophylline than were those produced by equipotent doses of dipyridamole and adenosine; the latter two were inhibited to a similar degree. With all three drugs, aminophylline produced parallel displacement of the dose-response curves consistent with competitive inhibition. These results with aminophylline may be relevant to the more powerful inhibition of platelet aggregation reported for RA233.
Footnotes
- Received February 7, 1972.
- Accepted June 2, 1972.
- © 1972, by The Williams & Wilkins Company
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