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 microM 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 effect was antagonised by 1 mM Ni2+, but not by 1 microM nifedipine. By contrast, at 40, 80 and 128 mM K+, BHQ antagonised Ca2+-induced contraction. This effect was partially reversed by 1 microM methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyri dine-5-carboxylate (Bay K 8644) or by increasing extracellular Ca2+ concentration. In the presence of nifedipine and Ni2+, depolarised rings (80 mM K+) contracted in response to addition of 1 microM 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 Ca2+ influx via a Ni2+-sensitive pathway, whereas its myolytic activity is due either to antagonism of Ca2+ entry via L-type Ca2+ channels or depletion of intracellular Ca2+ stores.
Fusi
F
F
Istituto di Scienze Farmacologiche, Università di Siena, Italy. fusif@unisi.it
Gorelli
B
B
Valoti
M
M
Marazova
K
K
Sgaragli
G P
GP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D002120:Calcium Channel Agonists; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D010656:Phenylephrine; C019359:2,5-di-tert-butylhydroquinone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000252:Calcium-Transporting ATPases; D002118:Calcium