(Hypertension. 1995;26:684-690.)
© 1995 American Heart Association, Inc.
Articles |
Relationship of Arachidonic Acid Release to Porcine Coronary Artery Relaxation
From the Departments of Internal Medicine (N.L.W., R.S.S., L.M., A.J.L.) and Pharmacological and Physiological Science (A.H.S., A.J.L.), St Louis (Mo) University School of Medicine.
Correspondence to Neal L. Weintraub, MD, St Louis University School of Medicine, Division of Clinical Pharmacology, Room M205, 1402 S Grand Blvd, St Louis, MO 63104.
Abstract 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 µmol/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 µmol/L) U73122 abolished both bradykinin-induced, EDHF-mediated relaxation and prostaglandin I2 production. Similarly, the calcium-ATPase inhibitor thapsigargin, given at a dose (1 µmol/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. Moreover, EDHF production in porcine coronary artery appears to be closely associated with arachidonic acid release, thus supporting the hypothesis that arachidonic acid, acting through a cyclooxygenase-independent mechanism, is responsible for EDHF production in porcine coronary artery.
Key Words: endothelium-derived factors • epoprostenol • nitric oxide • phospholipase C • arachidonic acid • arteries • phospholipases A
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