Responses of Human Basilar and Other Isolated Arteries to Novel Nitric Oxide Donors

Abstract

The adducts of nitric oxide (NO), diethylamine/NO (DEA/NO) and diethylenetriamine/NO (DETA/NO), are new NO donors that spontaneously release NO in aqueous solutions. These donors may have therapeutic advantages over sodium nitroprusside (SNP), which depends on metabolism to yield NO. This study was performed to define and compare the pharmacodynamic properties of these NO donors on isolated rings of human, canine, and porcine basilar arteries and further to compare canine and porcine common carotid arteries precontracted with KCl. The median effective concentration (EC50) and the basic effect of 100 microM were determined for each NO donor. On basilar arteries, DEA/NO was the most potent but the maximal dilatation produced by 100 microM did not persist for 60 min, whereas that of DETA/NO and SNP did. DETA/NO was more potent than SNP on all three species of basilar arteries but was the least potent on peripheral (carotid) arteries. Methylene blue in equimolar concentrations significantly inhibited the vasorelaxant effects of DEA/NO and DETA/NO, suggesting a common mechanism of action. Of the NO donors studied, the pharmacodynamic properties of DETA/NO seemed most relevant clinically as a cerebrovascular dilator in being more potent than SNP while producing sustained vasorelaxation.