2,5-di-t-butyl-1,4-benzohydroquinone induces endothelium-dependent relaxation of rat thoracic aorta

The aim of this work was to clarify the mechanism by which 2,5-di-t-butyl-1 ,4-benzohydroquinone (BHQ) induces relaxation of rat thoracic aorta. Tn par ticular, the role of endothelium-derived nitric oxide (NO) was investigated . BHQ concentration dependently (0.1-10 mu M) relaxed rat aorta rings preco ntracted with phenylephrine. This effect was dependent on the intactness of the endothelium, suppressed by preincubation with 100 mu M N omega-nitro-L -arginine methyl ester and antagonised by 3-30 mu M methylene blue. The 10 mu M BHQ-induced relaxation, however, was followed by the gradual and slow return to phenylephrine-induced tone. Superoxide dismutase (250 U/ml) incre ased the BHQ-induced relaxation, while preincubation with 3 mM diethyldithi ocarbamate inhibited it in a time-dependent fashion. BHQ gave rise to super oxide anion formation which was markedly inhibited by the addition of super oxide dismutase (250 U/ml), either in the presence or in the absence of aor ta rings. The non-specific blocker of Ca2+ channels, Ni2+, concentration de pendently attenuated the BHQ relaxing effect. BHQ did not modify the relaxa tion induced by the NO donor 3-morpholino-sydnonimine in endothelium-depriv ed rings. In conclusion, BHQ induces endothelium-dependent relaxation and g ives rise, by auto-oxidation, to the formation of superoxide anion. The for mer effect results from the enhanced synthesis of NO rather than from its e nhanced biological activity; NO synthase is presumed to be stimulated by BH Q-induced activation of Ca2+ influx through Ni2+-sensitive Ca2+ channels. ( C) 1999 Elsevier Science B.V. All rights reserved.