CARDIOVASCULAR EFFECTS OF AN ULTRA-SHORT-ACTING NITRIC OXIDE-RELEASING COMPOUND, ZWITTERIONIC DIAMINE NO ADDUCT, IN DOGS/

Background This study was conducted to clarify the cardiovascular effe cts of a new NO-releasing compound, NOC-7, and to compare it with othe r nitrovasodilators, sodium nitroprusside (SNP) and nitroglycerin, in dogs anesthetized with pentobarbital. Methods and Results A bolus inje ction of NOC-7 decreased mean aortic blood pressure in a dose-dependen t manner. The onset was rapid and the recovery quick. Continuous infus ion of NOC-7 decreased mean aortic pressure from 115+/-3.9 to 84+/-2.9 mm Hg and infusion of SNP, from 118+/-3.8 to 87+/-3.1 mm Hg. The opti mum doses of NOC-7 and SNP were determined to be 2.73+/-0.77 and 11.5/-6.1 mu g . kg(-1) . min(-1), respectively. During infusion of NOC-7, heart rate and cardiac output were increased (P<.05), pulmonary arter y pressure was not changed, and systemic and pulmonary vascular resist ances were decreased (P<.05). Electromagnetic flowmetry showed that po rtal Venous and internal carotid arterial blood flow were increased (P <.05) and that hepatic and renal arterial blood flows were not changed . These hemodynamic changes during NOC-7 infusion were similar to thos e with SNP. The plasma level of NO2-/NO3- did not change, but methemog lobin increased slightly (P<.05). Comparison between hypotensive respo nses before and after a 3.5- hour infusion of NOC-7 or nitroglycerin s howed that acute tolerance developed to nitroglycerin but not to NOC-7 . Conclusions The results indicate that NOC-7 may be useful as an ultr a-short-acting nitrovasodilator that has no major adverse effect or to lerance.