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.
Bassenge
E
E
Institute of Applied Physiology, University of Freiburg, Germany.
Zanzinger
J
J
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007260:Infusion Pumps; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D013558:Sydnones / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D013558:Sydnones; D014665:Vasodilator Agents; C072857:3-(cis-2,6-dimethylpiperidino)sydnonimine; D005996:Nitroglycerin; D006152:Cyclic GMP