Stimulation of long-chain fatty acid uptake by dipyridamole in isolated myocytes

This study was designed to investigate the effects of the cardiovascular dr ug dipyridamole on fatty acid metabolism in isolated cardiac myocytes. Effe cts of dipyridamole on the oxidation of long-chain (palmitate) fatty acid, medium-chain (octanoate) fatty acid, and the carbohydrate intermediate (pyr uvate) were determined by using isolated cardiac myocytes from both normal and diabetic rats. Dipyridamole increased palmitate oxidation in a concentr ation-dependent manner in both normal and diabetic myocytes. Maximal stim u lation of palmitate oxidation (175% of control) was observed with 100 mu M dipyridamole. In contrast, oxidation of octanoate and pyruvate was not affe cted. The stimulation of palmitate oxidation by dipyridamole persisted desp ite its removal from the incubation medium. In contrast to the effect in my ocytes, palmitate oxidation was not affected by dipyridamole in isolated ra t heart mitochondria. Palmitate uptake was increased by 2.5- and 1.6-fold w hen palmitate concentration was adjusted to 0.05 and 0.2 mM, respectively. Dipyridamole did not affect lipolysis in isolated myocytes. When dipyridamo le (100 mu M) and L-carnitine (5 mM) were added together to the incubation medium, palmitate oxidation was further increased to 223% of the control. T he nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR) failed to increase palmitate oxidation in isolated myocytes. Although palmitate oxida tion in diabetic cells is much higher than that in normal myocytes, dipyrid amole increased palmitate oxidation by 243% in diabetic myocytes over its b aseline oxidation rate in normal cells. These results suggest that increase d palmitate oxidation in isolated cardiac myocytes after dipyridamole admin istration occurs independent of effects on either the phosphodiesterase enz yme or nucleoside transport protein, but it may result from increased palmi tate transport across the plasma membrane.