RESPONSES OF HUMAN BASILAR AND OTHER ISOLATED ARTERIES TO NOVEL NITRIC-OXIDE DONORS

The adducts of nitric oxide (NO), diethylamine/NO (DEA/NO) and diethyl enetriamine/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 pharmacodynami c properties of these NO donors on isolated rings of human, canine, an d porcine basilar arteries and further to compare canine and porcine c ommon carotid arteries precontracted with KCl. The median effective co ncentration (EC50) and the basic effect of 100 mu M were determined fo r each NO donor. On basilar arteries, DEA/NO was the most potent but t he maximal dilatation produced by 100 mu M 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 concentrati ons significantly inhibited the vasorelaxant effects of DEA/NO and DET A/NO, suggesting a common mechanism of action. Of the NO donors studie d, the pharmacodynamic properties of DETA/NO seemed most relevant clin ically as a cerebrovascular dilator in being more potent than SNP whil e producing sustained vasorelaxation.