8-bromocyclic-gmp and ebselen

The effect of 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) on nitric oxide (NO) mediated responses and NO generation from NO donors were studied in vitro. In precontracted rat isolated anococcygeus muscles, relaxations induced by NO donors, electrical field stimulation and 5-[1-(phenylmethyl)-1H-indazole-3-yl]-2-furanmethanol (YC-1) were significantly inhibited by ebselen (100 microM), whereas responses elicited by papaverine and theophylline were not affected; those by 8-bromo-cyclic-guanosine-monophosphate (8-Br-cGMP) were slightly enhanced. NO generation from NO gas aqueous solution or acidified nitrite was not affected, but that from S-nitroso-N-acetyl-penicillamine (SNAP) was attenuated by ebselen, and the attenuation was reserved by glutathione. Both glutathione and cupric sulphate altered the ultraviolet spectrum of ebselen. These findings suggest that ebselen at high concentrations nonselectively inhibited NO-mediated responses, possibly through inhibiting soluble guanylate cyclase. Ebselen does not appear to directly interact with NO, but it may inhibit NO release from nitrosothiols by a thiol- and/or copper-dependent mechanism.

Topics: Animals; Aorta; Azoles; Copper; Cyclic GMP; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Electric Stimulation; Endothelium, Vascular; Enzyme Activators; Enzyme Inhibitors; Glutathione; In Vitro Techniques; Indazoles; Isoindoles; Male; Muscle Relaxation; Muscle, Smooth; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitroprusside; Organoselenium Compounds; Papaverine; Penicillamine; Phosphodiesterase Inhibitors; Rats; Rats, Sprague-Dawley; Spectrophotometry, Ultraviolet; Vasodilation