European Journal of Pharmacology, 72 (1981) 57--61 57 Elsevier/North-Holland Biomedical Press ATTENUATION BY ACETAMINOPHEN OF ARACHIDONIC ACID-INDUCED CORONARY VASODILATION AND OUTPUT OF PROSTAGLANDINS IN THE ISOLATED RAT HEART JOEL E. SHAFFER, LAUREN M. CAGEN and KAFAIT U. MALIK Department of Pharmacology, University of Tennesse Center for the Health Sciences, Memphis, TN 38163, U.S.A. Received 22 January 1981, revised MS received 25 March 1981, accepted 26 March 1981 J.E. SHAFFER, L.M. CAGEN and K.U. MALIK, Attenuation by acetaminophen of arachidonic acid-induced coronary vasodilation and output of prostaglandins in the isolated rat heart, European J. Pharmacol. 72 (1981) 57--61. We studied the effect of acetaminophen on the vascular actions of arachidonic acid and on the output of pros- taglandins in the isolated rat heart. Arachidonic acid (33 nmol), administered as a bolus into the heart through the aortic cannula produced vasoconstriction followed by a long lasting vasodilation. Arachidonic acid also markedly increased the output of PGE 2 and 6-keto-PGFl~ from the heart. In the presence of acetaminophen (0.1--1.0 raM) both the output of .prostaglandins and the duration of the coronary vasodilation were attenuated. We suggest that the major component of arachidonic acid-induced coronary vasodilation is mediated through prostaglandin synthesis and is blocked by acetaminophen. Isolated rat heart Radioimmunoassay Acetaminophen PGE2 Arachidonic acid 6-keto-PGF1 1. Introduction Acetaminophen is an analgesic and anti- pyretic drug with minimal anti-inflammatory activity in man. This distinction in thera- peutic activity has been attributed to the greater potency of acetaminophen to inhibit prostaglandin synthesis in the brain than in peripheral tissues (Flower and Vane, 1972). However, there are several reports suggesting that acetaminophen inhibits prostaglandin formation in peripheral tissues. For example, acetaminophen has been shown to block the PGE2 synthesis in rat renal slices (Zenser et al., 1978; Mattammal et al., 1979). In addi- tion, Damas and Mousty (1978) have reported that acetaminophen blocks the hypotensive action of arachidonic acid in rats. The pur- pose of this study was to determine whether or not acetaminophen alters the vasodilator response of coronary vessels to arachidonic acid by affecting prostaglandin synthesis. 2. Materials and methods 2.1. Perfusion of isolated rat hearts Male Sprague-Dawley rats weighing 200-- 250 g (Charles River Breeders)were anesthe- tized with ether, the abdomen opened and heparin (1000 U/kg, i.v.) administered. After thoracotomy, the heart was quickly removed and placed in ice cold saline. A cannula was inserted into the aorta and the heart placed in a warmed chamber and perfused at a rate of 6 ml/min with a Harvard peristaltic pump (model 1203) with oxygenated (5% CO: in O2) Krebs-Henseleit solution composed of (mM) NaC1 114.2, KC1 4.7, KH2PO4 1.2, 0 014-2999/81/0000--0000/$02.50 © Elsevier/North-Holland Biomedical Press