Effectiveness of an NO-releasing pirsidomine derivative on coronary conductance during long-term administration.

Nitrovasodilators have long been used in the treatment of myocardial ischemia. One of the limitations of their chronic administration is loss of drug action over time. Nitrovasodilator-induced drug tolerance results from either the loss of cyclic guanosine monophosphate-dependent dilator effects, or from biological counterregulatory processes, usually neurohormonal adaptations. C87-3754, a derivative of pirsidomine, is a new nitric oxide-releasing sydnonimine. Continuous 5-day infusion of C87-3754 in dogs did not result in a substantial loss of drug action. There was long-lasting dilation evident in the large coronary arteries and venous bed, resulting in improved coronary conductance. Administration of C87-3754 was associated with reduction in cardiac preload, wall stress, and subendocardial tissue pressure.