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-ben zohydroquinone (BHQ) on vascular smooth muscle, the different effects of BHQ on rat aorta were investigated under several experimental condi tions. In aortic rings at rest or depolarised with 80 mM K+ in the pre sence of 1 mu M nifedipine, BHQ evoked a slow tonic contraction which was antagonised by 1 mM Ni2+. Depolarised rings contracted in response to addition of 1 mM Ca2+, with an EC50 value of 32.4 +/- 1.0 mM for K +. At 20 mM K+, Ca2+-induced contraction was enhanced by BHQ. This eff ect was antagonised by 1 mM Ni2+, but not by 1 mu M nifedipine. By con trast, at 40, 80 and 128 mM K+, BHQ antagonised Ca2+-induced contracti on. This effect was partially reversed by 1 mu M -(2-trifluorornethylp henyl)-pyridine-5-carboxylate (Bay K 8644) or by increasing extracellu lar Ca2+ concentration. In the presence of nifedipine and Ni2+, depola rised rings (80 mM K+) contracted in response to addition of 1 mu M ph enylephrine; this response was fast and then slowly decreased. When th e preparations were preincubated with BHQ, the phenylephrine-induced c ontraction 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 Ca2+ influx via a Ni2+-se nsitive pathway, whereas its myolytic activity is due either to antago nism of Ca2+ entry via L-type Ca2+ channels or depletion of intracellu lar Ca2+ stores. (C) 1998 Elsevier Science B.V.