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

• Published in: European journal of pharmacology 1999-02, Vol.366 (2), p.181-187
• Main Authors: Fusi, Fabio, Valoti, Massimo, Frosini, Maria, Sgaragli, Gian P.
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; BHQ (2,5-di- t-butyl-1,4-benzohydroquinone); Biological and medical sciences; Ca 2+ channel, Ni 2+-sensitive; Cardiovascular system; Chelating Agents - pharmacology; Ditiocarb - pharmacology; Dose-Response Relationship, Drug; Endothelium, Vascular - physiology; Enzyme Inhibitors - pharmacology; Free Radical Scavengers - pharmacology; Hydroquinones - pharmacology; In Vitro Techniques; Male; Medical sciences; Molsidomine - analogs & derivatives; Molsidomine - pharmacology; Muscle Relaxation - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nickel - pharmacology; Nitric oxide (NO); Pharmacology. Drug treatments; Phenylephrine - pharmacology; Rats; Rats, Wistar; Superoxide anion; Superoxide Dismutase - pharmacology; Superoxides - metabolism; Vasoconstrictor Agents - pharmacology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00932-7

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. In particular, the role of endothelium-derived nitric oxide (NO) was investigated. BHQ concentration dependently (0.1–10 μM) relaxed rat aorta rings precontracted with phenylephrine. This effect was dependent on the intactness of the endothelium, suppressed by preincubation with 100 μM Nω-nitro- l-arginine methyl ester and antagonised by 3–30 μM methylene blue. The 10 μM BHQ-induced relaxation, however, was followed by the gradual and slow return to phenylephrine-induced tone. Superoxide dismutase (250 U/ml) increased the BHQ-induced relaxation, while preincubation with 3 mM diethyldithiocarbamate inhibited it in a time-dependent fashion. BHQ gave rise to superoxide anion formation which was markedly inhibited by the addition of superoxide dismutase (250 U/ml), either in the presence or in the absence of aorta rings. The non-specific blocker of Ca 2+ channels, Ni 2+, concentration dependently attenuated the BHQ relaxing effect. BHQ did not modify the relaxation induced by the NO donor 3-morpholino-sydnonimine in endothelium-deprived rings. In conclusion, BHQ induces endothelium-dependent relaxation and gives rise, by auto-oxidation, to the formation of superoxide anion. The former effect results from the enhanced synthesis of NO rather than from its enhanced biological activity; NO synthase is presumed to be stimulated by BHQ-induced activation of Ca 2+ influx through Ni 2+-sensitive Ca 2+ channels.