Effects of dipyridamole on the glyceryl-trinitrate-induced inhibition of coronary artery muscle tone and platelet aggregation in relation to cyclic nucleotide metabolism.

Abstract

The effects of glyceryl-trinitrate (GTN) and dipyridamole (DIP) on relaxation of bovine coronary arteries and on inhibition of aggregation of human platelets have been studied in vitro with special reference to the cyclic GMP (cGMP) system. GTN had a dose-dependent relaxant effect on bovine coronary arteries, and at a high concentration (10(-5) M) it had an inhibiting effect on platelet aggregation. The effects were associated with an increase in the cGMP levels of the tissues. DIP (5 X 10(-7) M respectively 5 X 10(-6) M) potentiated the coronary artery relaxation induced by GTN (10(-8) M) and the inhibition of platelet aggregation caused by GTN in the concentrations 10(-7)-10(-4) M. The potentiation was associated with higher levels of cGMP than those produced by GTN alone, at least in bovine coronary arteries. However, at a concentration of 10(-4) M, GTN, in combination with DIP, caused a significant fall in the cGMP level compared to GTN alone. GTN and DIP were not found to significantly increase the cAMP levels in the concentrations tested. DIP was shown to inhibit phosphodiesterase (PDE) from both platelets and bovine coronary arteries. This might be one of the possible mechanisms that can explain the above mentioned potentiation. It is suggested that the combination of DIP + GTN may be of some clinical importance since the potentiating effects were seen at concentrations comparable to the therapeutic plasma concentration for the respective drugs.