Inhibition of the Different Phosphodiesterase Isoforms of Rat Heart Cytosol by Free Fatty Acids

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Abstract
The sensitivity of the various phosphodiesterase (PDE) isoforms present in the cytosolic compartment of rat heart to the main fatty acids of the saturated, n-3 and n-6 families was assessed. High-performance liquid chromatography (HPLC) on a Mono Q ion-exchange column resolved four separate cyclic nucleotide phosphodiesterase activities: a calmodulin-activated fraction, a cyclic GMP-stimulated fraction, a cyclic AMP-specific rolipram-sensitive fraction, and a cyclic GMP-inhibited fraction. Polyunsaturated fatty acids (PUFA) were more potent inhibitors than saturated fatty acids whatever the considered PDE isoform. Although all PDE isoforms were affected, the cyclic GMP-stimulated isoform was the most sensitive to the inhibitory effect of PUFAs. The possible influences of free fatty acids (FFA) on cardiac contractility through PDE inhibition are discussed.

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