Relationship of arachidonic acid release to porcine coronary artery relaxation.
In porcine coronary artery endothelium-dependent relaxation to bradykinin is in part attributed to a chemically unidentified factor, termed endothelium-derived hyperpolarizing factor (EDHF). We hypothesize that arachidonic acid, acting through a cyclooxygenase-independent mechanism, is responsible for EDHF production. To define the relationship between EDHF production and arachidonic acid release, we investigated the role of phospholipase C in bradykinin-induced relaxation and prostaglandin I2 production (an index of arachidonic acid release) in porcine coronary artery. The phospholipase C inhibitor U73122 (1 mumol/L) abolished bradykinin-induced, nitric oxide-mediated relaxation but did not inhibit either bradykinin-induced, EDHF-mediated relaxation or prostaglandin I2 production. However, when given at a larger dose (20 mumol/L) U73122 abolished both bradykinin-induced, EDHF-mediated relaxation and prostaglandin I2 production. Similarly, the calcium-ATPase inhibitor thapsigargin, given at a dose (1 mumol/L) that abolished bradykinin-induced increases in intracellular calcium concentration in cultured porcine coronary artery endothelial cells, eliminated both bradykinin-induced. EDHF-mediated relaxation and prostaglandin I2 production. Although thapsigargin abolished bradykinin-induced prostaglandin I2 production, the basal production of prostaglandin I2 was enhanced and contraction of endothelium-intact rings was attenuated. These latter responses are most likely related to enhanced basal arachidonic acid release and associated EDHF production. These observations suggest that phospholipase C activation and increased intracellular calcium concentration are required for both bradykinin-induced arachidonic acid release and EDHF production in porcine coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Weintraub
N L
NL
Department of Internal Medicine, St. Louis (Mo) University School of Medicine 63104, USA.
Stephenson
A H
AH
Sprague
R S
RS
McMurdo
L
L
Lonigro
A J
AJ
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D001158:Arteries / Q000502:physiology; D001685:Biological Factors / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis; D004963:Estrenes / Q000494:pharmacology; D066298:In Vitro Techniques; D011760:Pyrrolidinones / Q000494:pharmacology; D013552:Swine; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D001685:Biological Factors; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; D013729:Terpenes; C067410:endothelium-dependent hyperpolarization factor; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D016718:Arachidonic Acid; D019284:Thapsigargin; D011464:Epoprostenol; D010738:Type C Phospholipases; D001920:Bradykinin