Extracellular and intracellular arachidonic acid-induced contractions in rat aorta.
Arachidonic acid induced contractions of de-endothelized rat aortic rings. A more potent effect was obtained after intracellular administration of arachidonic acid using liposomes. Contractions induced by extracellular arachidonic acid were inhibited similarly to phenylephrine-induced contractions by the L-type Ca2+ channel blocker, methoxyverapamil (D600), and the calmodulin inhibitor, calmidazolium. In contrast, contractions induced by arachidonic acid-filled liposomes were not affected by these compounds. Indomethacin did not affect the contractions induced by either extra- or intracellular arachidonic acid, whereas nordihydroguaiaretic acid relaxed contractions induced by extracellular arachidonic acid but not those induced by arachidonic acid-filled liposomes. Apart from a relaxing effect on contractions induced by extracellular arachidonic acid or by phenylephrine, protein kinase C inhibition 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 contractile effect on rat aorta, and this effect is regulated differently depending on the site of application.
Groningen Institute for Drug Studies, Department of Clinical Pharmacology, University of Groningen, Netherlands.
C M
CM
Filipeanu
E
E
Brailoiu
G
G
Petrescu
S A
SA
Nelemans
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002855:Chromatography, Thin Layer; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008081:Liposomes; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010539:Permeability; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D008081:Liposomes; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D011493:Protein Kinase C