NO donor and biological properties of different benzofuroxans

Purpose. To investigate the effect of benzofusion on NO donor properties an d related biological activities of the furoxan system. The biological prope rties considered were the ability to increase the cytosolic levels of cCMP in C6 cells and vasodilation. Methods. NO donor properties were investigated either in the presence or th e absence of cysteine by using the Griess reaction, chemiluminescence, and gas chromatography. Increase of cytosolic cGMP levels were evaluated by rad ioimmunoassay. Vasodilating activity was assessed on rat aorta strips preco ntracted with noradrenaline, in the presence and the absence of oxyhemoglob in (HbO(2)) and methylene blue (MB), respectively. Results. Benzofuroxan and its methyl and cyano derivatives were unable to r elease NO under the experimental conditions. Generally these compounds disp layed feeble vasodilating properties and were able to weakly stimulate solu ble guanylate cyclase (sGC). By contrast, benzodifuroxan and benzotrifuroxa n were able to produce both NO. and its reduced form NO-, the nitroxyl anio n. They displayed potent vasodilating properties and were able to increase cytosolic levels of cGMP in a concentration-dependent manner. Conclusions. The simple benzofuroxans considered here are devoid of the cap ability to release NO, they weakly stimulate sGC as well as manifest feeble vasodilating properties by a mechanism that does not involve a thiol-induc ed NO production. By contrast, benzodifuroxan and benzotrifuroxan behave as typical NO donor furoxans.