Effects of 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ) on rat aorta smooth muscle

To characterise the pharmacological activity of 2,5-di- t -butyl-1,4-benzohydroquinone (BHQ) on vascular smooth muscle, the different effects of BHQ on rat aorta were investigated under several experimental conditions. In aortic rings at rest or depolarised with 80 mM K + in the presence of 1 μ M nifedipine, BHQ evoked a slow tonic contraction which was antagonised by 1 mM Ni 2+ . Depolarised rings contracted in response to addition of 1 mM Ca 2+ , with an EC 50 value of 32.4±1.0 mM for K + . At 20 mM K + , Ca 2+ -induced contraction was enhanced by BHQ. This effect was antagonised by 1 mM Ni 2+ , but not by 1 μ M nifedipine. By contrast, at 40, 80 and 128 mM K + , BHQ antagonised Ca 2+ -induced contraction. This effect was partially reversed by 1 μ M methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate (Bay K 8644) or by increasing extracellular Ca 2+ concentration. In the presence of nifedipine and Ni 2+ , depolarised rings (80 mM K + ) contracted in response to addition of 1 μ M phenylephrine; this response was fast and then slowly decreased. When the preparations were preincubated with BHQ, the phenylephrine-induced contraction was transient and antagonised in a concentration-dependent manner by BHQ. These results indicate that the myotonic effect of BHQ on rat aortic rings depends on activation of Ca 2+ influx via a Ni 2+ -sensitive pathway, whereas its myolytic activity is due either to antagonism of Ca 2+ entry via L-type Ca 2+ channels or depletion of intracellular Ca 2+ stores.