Reversal of nitroglycerin tolerance in vitro by the cGMP-phosphodiesterase inhibitor zaprinast.

Following in vitro exposure of rat aortic rings to 550 microM nitroglycerin for 1 h, tolerance was demonstrated by a significant increase in EC50 values for nitroglycerin-induced relaxation. However, cross-tolerance to sodium nitroprusside was not observed. Co-incubation of aortic rings with the cGMP-phosphodiesterase (cGMP-PDE) inhibitor zaprinast (10 microM), during incubation with 550 microM nitroglycerin, did not prevent the development of tolerance.