Effects of ranolazine on oxidative substrate preference in
epitrochlearis muscle.
McCormack, James G., Vickie E. Baracos, Rick Barr, and Gary D.
Lopaschuk.
Department of Pharmacology, Syntex Research Centre, Heriot-Watt
University Research Park, Riccarton, Edinburgh, Scotland, UK,
Department of Agricultural, Food and Nutritional Sciences, University
of Alberta, Edmonton, Canada, Departments of Pediatrics and
Pharmacology, 423 Heritage Medical Research Center, University of
Alberta, Edmonton, Canada
APStracts 3:0160A, 1996.
Ranolazine is an novel investigational anti-anginal agent which
stimulates glucose oxidation in isolated rat hearts. This study
determined its effects on metabolic substrate and O2 utilization in
an in vitro skeletal muscle preparation, the rat epitrochlearis
muscle. Muscles were superfused with Krebs'-Henseleit buffer
containing 3% albumin, 0.4mM palmitate, 5.5mM glucose, 0.5mM lactate
and a physiological amino acid mixture. Perfusate also contained
either (i) [U-14C]-glucose for measurement of glucose oxidation, or
(ii) [9,10-3H]-palmitate and [U-14C]-lactate for measurement of
palmitate and lactate oxidation. Addition of ranolazine (10 [mu]M)
significantly stimulated glucose oxidation and decreased palmitate
oxidation, but had no effect on lactate oxidation. Overall, the
calculated relative contribution of glucose oxidation to aerobic ATP
production increased from 12% to 33%, whereas from palmitate it
decreased from 55% to 26%. Ranolazine did not alter tissue malonyl
CoA contents, making it unlikely that the decrease in palmitate
oxidation caused by ranolazine is due to a decrease in the activity
of acetyl CoA carboxylase. These data demonstrate that ranolazine can
shift energy substrate preference in skeletal muscle, which could
potentially prove useful in ischemic disorders of skeletal muscle.
Received 28 September 1995; accepted in final form 14 March 1996.
APS Manuscript Number A1045-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96