Abstract
PAF-acether caused a dose-related decrease in blood pressure of conscious SHR rats (5–20 μg/kg i.p.) and anaesthetized normotensive rats (0.06–0.50 μg/kg i.v.). In anaesthetized normotensive rats, PAF-acether-induced hypotension was not associated with tachycardia and not modified by various pretreatments such as atropine, mepyramine, cimetidine, propranolol, sulpiride, ketoprofen (an inhibitor of prostaglandin cyclooxygenase) and teprotide. PAF-acether (0.5 μg/kg i.v.) reduced the pressor effect of norepinephrine but not that of angiotensine II.
In pithed rats, PAF-acether (0.12–0.50 μg/kg i,.v.) shifted the dose-response curve for norepinephrine-induced hypertension to the right in a parallel manner and did not reverse the inhibitory action of clonidine on cardiac nerve stimulation.
These results suggest that the hypotensive effect of PAF-acether in anaesthetized rats may be mediated by α-adrenergic blockade and PAF-acether looks like a powerful postsynaptic adrenoceptor blocking agent.
However,in vitro, up to 100 μg/l, PAF-acether did not modify the norepinephrine-induced contractions on non-vascular (vas deferens) and vascular (thoracic aorta) preparations of rats. Moreover, PAF-acether did not inhibitin vitro [3H]WB-4101 and [3H]p-aminoclonidine binding in rat brain preparations.
This absence ofin vitro activity suggest that thein vivo adrenolytic activity of PAF-acether is in fact an indirect one either via a directly active metabolite or possibly through the release of an unidentified endogenous adrenolytic factor.
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Caillard, C.G., Mondot, S., Zundel, J.L. et al. Hypotensive activity of PAF-acether in rats. Agents and Actions 12, 725–730 (1982). https://doi.org/10.1007/BF01965093
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DOI: https://doi.org/10.1007/BF01965093