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European Heart Journal 1984 5(3):253-260;
Copyright © 1984 by the European Society of Cardiology.
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© 1984 The European Society of Cardiology

Leukotriene D4-induced vasoconstriction of coronary arteries in anaesthetized dogs

V. B. FIEDLER, M. MARDIN and T.S. ABRAM*

Department of Pharmacology Bayer AG, Wupperlal, F.R.G
*Stoke Court Research, Miles Laboratory Slough, U.K.

Received 12 August 1983; revised 3 October 1983; .

Requests for reprints to. V.B. Fiedler, Bayer AG, Institut für Pharmakologie, Aprather Weg 18a, D-5600 Wuppertal 1 (Elberfeld). F.R.G.

Abstract

We examined in pentobarbital-anaesthetized dogs, the effects of intracoronary leukotriene D4 (LTD4) on large vessel (circumflex artery) flow and diameter and on calculations of late diastolic and total coronary resistance. Heart rate, systolic and end-diastolic ventricular pressures and the dP/dt were the haemo-dynamic variables studied. The peripheral ECG was obtained in lead II. LTD4 (0.l-l0/µg kg–1) reduced coronary diameter up to 12±3% (mean±s.e.m.). Coronary flow decreased in dose-dependent fashion up to 100%. Blood flow returned to control values within 3-15 min of LTD4 administration. Blood pressure, heart rate and ventricular pressure did not change while LV dP/dtmax fell and filling pressure increased. The sum of ST segments and R wave voltages of the ECG increased indicating transient myocardial ischaemia during LTD4 induced coronary blood flow cessation. Small vessel and total coronary resistance rose in a dose-dependent manner between 33-232% and 50-500%, respectively. Inhibition of cyclo-oxygenase enzyme (indomethacin, 5 mg kg–1 i.v.) and lipoxygenase enzymes (nafazatrom, 10 mg kg–1, i.d.J had no effect on LTD4-caused alterations in coronary flow, resistance and arterial diameter. Thus, in canine experiments the intracoronary administration of LTD4 can constrict coronary arteries presumably large conductive vessels. This is independent of the cyclooxygenase and additional lipoxygenase metabolites of the arachidonic acid pathway other than LTD4. Therefore, the agent may contribute to cardiac dysfunction in coronary artery disease and spasm.

Key Words: Dog • leukotriene D4 • coronary artery • coronary arterial diameter • vasoconstriction • coronary resistance • electrocardiography • indomethacin • nafaxatrom


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