Cardiovascular effects of an ultra-short-acting nitric oxide-releasing compound, zwitterionic diamine/NO adduct, in dogs.

Abstract

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. 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 micrograms.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 NO2-/NO3 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. The results indicate that NOC-7 may be useful as an ultra-short-acting nitrovasodilator that has no major adverse effect or tolerance.