EXTRACELLULAR AND INTRACELLULAR ARACHIDONIC ACID-INDUCED CONTRACTIONSIN RAT AORTA

Arachidonic acid induced contractions of de-endothelized rat aortic ri ngs. A more potent effect was obtained after intracellular administrat ion of arachidonic acid using liposomes. Contractions induced by extra cellular arachidonic acid were inhibited similarly to phenylephrine-in duced contractions by the L-type Ca2+ channel blocker, methoxyverapami l (D600), and the calmodulin inhibitor, calmidazolium. In contrast, co ntractions induced by arachidonic acid-filled liposomes were not affec ted by these compounds. Indomethacin did not affect the contractions i nduced by either extra- or intracellular arachidonic acid, whereas nor dihydroguaiaretic acid relaxed contractions induced by extracellular a rachidonic acid but not those induced by arachidonic acid-filled lipos omes. Apart from a relaxing effect on contractions induced by extracel lular arachidonic acid or by phenylephrine, protein kinase C inhibitio n with 1-(5-isoquinolinesulphonyl-2-methylpiperazine (H7)) had an even more prominent relaxing effect on contractions induced by arachidonic acid-filled liposomes. Therefore, arachidonic acid exerts a contracti le effect on rat aorta, and this effect is regulated differently depen ding on the site of application. (C) 1998 Elsevier Science B.V. All ri ghts reserved.