SUPEROXIDE DOES NOT INHIBIT GLYCERYL TRINITRATE-RABBIT AORTIC STRIP-MEDIATED RELAXATION OF RABBIT TAENIA-COLI - EVIDENCE AGAINST A ROLE NITRIC-OXIDE ITSELF AS THE SMOOTH-MUSCLE ACTIVE-DRUG METABOLITE

This study was designed to test the hypothesis that nitric oxide (NO) is the relaxant metabolite produced by metabolic activation of glycery l trinitrate (GTN) in rabbit aortic strip (RAS). Superoxide anion, an inactivator of NO, was included in a two-tissue bioassay in which rabb it Taenia coli strip (RTCS) relaxed to GTN in the presence of RAS. Sup eroxide as generated by xanthine (10 mu M)/xanthine oxidase (20 mU/ml) failed to attenuate relaxations of RTCS to GTN (0.1 nM-10 mu M) and R AS, compared with the untreated control. In contrast, superoxide atten uated the relaxation of RTCS to both authentic NO gas and to SIN-1 (0. 1 nM-10 mu M), a known spontaneous releaser of NO; the attenuation of RTCS relaxation to NO gas was reversed by superoxide dismutase (100 un its/ml). In addition, another drug that has been reported to scavenge NO, hydroquinone, did not attenuate the RTCS relaxation to GTN. These results suggest that biotransformation of GTN in vascular smooth muscl e that leads to relaxation is caused by a NO-containing species (i.e. a S-nitrosothiol). Such a molecule would be less susceptible to inacti vation by superoxide anion and hydroquinone.