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(Circulation. 1996;94:2235-2240.)
© 1996 American Heart Association, Inc.

Articles

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

Ping Zhang, MD; Akitoshi Ohara, MD; Takashi Mashimo, MD; Jianhua Sun, MD; Satoshi Shibuta, MD; Koji Takada, MD; Hiroaki Kosaka, MD; Masaru Terada, PhD; Ikuto Yoshiya, MD

the Department of Anesthesiology (P.Z., A.O., T.M., S.S., K.T., I.Y.), the First Department of Surgery (J.S.), the First Department of Physiology (H.K.), and the Department of Legal Medicine (M.T.), Osaka University Medical School, Japan.

Correspondence to Ping Zhang, Department of Anesthesiology, Osaka University Medical School, Yamadaoka 2-2, Suita City, Osaka 565, Japan.

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 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.

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

Key Words: endothelium-derived factors • vasodilation • nitroglycerin • hemodynamics

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