IN-VITRO BRONCHORELAXING EFFECTS OF NOVEL NITRIC-OXIDE DONORS GEA-3268 AND GEA-5145 IN GUINEA-PIGS AND RATS

Endogenously released nitric oxide (NO) in airways might contribute to physiological bronchodilation; induced production of NO might play a role in the pathogenesis of asthma, although it could also be a compen satory mechanism to other factors that cause bronchoconstriction or in flammation. To investigate the efficacy of NO donors on bronchial tone , the bronchorelaxing efficacies of NO donors, new experimental GEA co mpounds 3268 and 5145 (oxatriazole sulphonylamides) were compared with those of sodium nitroprusside and SIN-1 (3-morpholinosydnonimine) and to the standard beta(2)-adrenergic agonist, salbutamol, in bronchi of guinea-pigs and rats in-vitro. Their relaxing effects were also studi ed in rat mesentery arteries to compare the selectivity for airways. T he capacity of the NO donors to produce nitrites and nitrates was assa yed by the Griess reaction. The novel NO donors GEA 3268 and GEA 5145 were more potent bronchorelaxing agents than the old NO donors sodium nitroprusside and SIN-1. In guinea-pig bronchi, however, salbutamol wa s most potent. In rat bronchi the GEA compounds induced the strongest relaxation effect when compared with the old NO donors or with salbuta mol. The airway selectivity of the drugs studied decreased in the orde r of salbutamol, SIN-1, GEA 5145, GEA 3268, sodium nitroprusside. The nitrites and nitrates produced spontaneously did not correlate with th e efficacy of the relaxants. The results obtained suggest that NO is o nly partly responsible for the relaxation and the potency is dependent on the animal species and constricting agents used.