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 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.


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 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.


CONCLUSIONS
The results indicate that NOC-7 may be useful as an ultra-short-acting nitrovasodilator that has no major adverse effect or tolerance.
Department of Anesthesiology, Osaka University Medical School, Japan.
P
P
Zhang
A
A
Ohara
T
T
Mashimo
J
J
Sun
S
S
Shibuta
K
K
Takada
H
H
Kosaka
M
M
Terada
I
I
Yoshiya
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D006454:Hemoglobins / Q000378:metabolism; D007275:Injections, Intravenous; D008706:Methemoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology; D013997:Time Factors; D014226:Triazenes / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
C100973:(1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-3-aminopropyl)-3-methyl-1-triazene; D006454:Hemoglobins; D009573:Nitrites; D010108:Oxyhemoglobins; D011073:Polyamines; D014226:Triazenes; D014665:Vasodilator Agents; C008657:nitrosyl hemoglobin; D009599:Nitroprusside; D009569:Nitric Oxide; D008706:Methemoglobin; D005996:Nitroglycerin