Cardiovascular Effects of an Ultra–Short-Acting Nitric Oxide–Releasing Compound, Zwitterionic Diamine/NO Adduct, in Dogs

Abstract

Background This study was conducted to clarify the cardiovascular effects of a new NO-releasing compound, NOC-7, and to compare it with other nitrovasodilators, sodium nitroprusside (SNP) and nitroglycerin, in dogs anesthetized with pentobarbital. Methods and Results A bolus injection of NOC-7 decreased mean aortic blood pressure in a dose-dependent manner. The onset was rapid and the recovery quick. Continuous infusion 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 optimum doses of NOC-7 and SNP were determined to be 2.73±0.77 and 11.5±6.1 μg·kg −1 ·min −1 , respectively. During infusion of NOC-7, heart rate and cardiac output were increased ( P <.05), pulmonary artery pressure was not changed, and systemic and pulmonary vascular resistances were decreased ( P <.05). Electromagnetic flowmetry showed that portal 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 those with SNP. The plasma level of NO 2 − /NO 3 − did not change, but methemoglobin increased slightly ( P <.05). Comparison between hypotensive responses before and after a 3.5-hour infusion of NOC-7 or nitroglycerin showed that acute tolerance developed to nitroglycerin but not to NOC-7. Conclusions The results indicate that NOC-7 may be useful as an ultra–short-acting nitrovasodilator that has no major adverse effect or tolerance.