A comparison of the effects of TMB-8 and nifedipine on pressor responses to alpha 1- and alpha 2-adrenoceptor agonists in pithed rats.
TMB-8 has been characterized as an inhibitor of the release of Ca2+ from intracellular pools. We have studied the modification of the pressor responses to selective alpha 1-adrenoceptor agonists (methoxamine and phenylephrine), and to selective alpha 2-adrenoceptor agonists (B-HT 920 and B-HT 933) in pithed rats, produced by TMB-8. We have compared this modification with that produced by the calcium antagonist nifedipine. Nifedipine (100 micrograms/kg, 300 micrograms/kg, and 1000 micrograms/kg) inhibited in a dose-dependent manner the pressor responses to the alpha 1- and alpha 2-adrenoceptor agonists, the dose-response curves to the alpha 2-adrenoceptor agonists being shifted further to the right. TMB-8 at a dose of 3000 micrograms/kg did not modify the pressor effects of the alpha 1-adrenoceptor agonists, and neither did it reinforce the inhibition of such responses produced by nifedipine. By contrast, TMB-8 pretreatment (0.03 micrograms/kg, 0.3 micrograms/kg, 3 micrograms/kg, 30 micrograms/kg, 300 micrograms/kg and 3000 micrograms/kg) inhibited the responses to both alpha 2-adrenoceptor agonists, the inhibition being more pronounced with B-HT 920. A similar effect was obtained with 0.03 micrograms/kg TMB-8 and 0.3 microgram/kg TMB-8, particularly in the case of B-HT 920. It was stronger with higher doses, but similar for all doses over 3 micrograms/kg. The inhibition of the pressor responses mediated by the stimulation of alpha 2-adrenoceptors by TMB-8 was less in rats treated with the Ca2+ entry promoter BAY K 8644 (300 micrograms/kg), and could also be reduced by the continuous infusion of CaCl2 (0.25 microgram/min).(ABSTRACT TRUNCATED AT 250 WORDS)
Aleixandre
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MA
Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain.
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D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D001381:Azepines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C024763:talipexole; D008729:Methoxamine; D009543:Nifedipine