EP(3) RECEPTOR-MEDIATED INHIBITION OF THE NEUROGENIC VASOPRESSOR RESPONSE IN PITHED RATS

In pithed rats, we studied the effects of prostaglandin E(2) and of subtype-selective prostaglandin E receptor (EP receptor) ligands on the rise in blood pressure induced by electrical stimulation of the preganglionic sympathetic nerves. Prostaglandin E(2), the EP(1)/EP(3) receptor agonist sulprostone and the EP(2)/EP(3) receptor agonist misoprostol inhibited the electrically induced increase in diastolic blood pressure (rank order of potencies sulprostone greater than or equal to misoprostol greater than or equal to prostaglandin E(2)); the rise in blood pressure induced by exogenously added noradrenaline was not affected by these compounds. The inhibitory effect of sulprostone on the electrically induced vasopressor response was not significantly changed by indomethacin. Iloprost (an agonist at EP(1) and prostacyclin receptors (IP receptors)) failed to affect the electrically evoked increase in blood pressure. The present study suggests that prostaglandin E(2) inhibits the release of catecholamines in pithed rats via prostanoid receptors of the EP(3) subtype, probably located presynaptically on the postganglionic sympathetic nerve fibres.