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)