Inhibition of the different phosphodiesterase isoforms of rat heart cytosol by free fatty acids.

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.