Modulation of beta-adrenergic receptor-stimulated lipolysis in the heart by prostaglandins

Abstract

The purpose of the present study was to investigate the contribution of prostaglandins to lipolysis elicited by beta-adrenergic receptor activation in the heart. We have studied the effect of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), and their precursor arachidonic acid (AA) in the presence and absence of a cyclooxygenase inhibitor, sodium meclofenamate, on glycerol output elicited by stimulation of beta-adrenergic receptors in the isolated rabbit heart with isoproterenol (ISOP). Bolus injections of ISOP (475 pmol) produced a constant increase in glycerol and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output. Infusion of sodium meclofenamate (16 microM) reduced basal and attenuated ISOP-induced 6-keto-PGF1 alpha output and enhanced glycerol output. During inhibition of endogenous prostaglandin synthesis with meclofenamate, infusion of PGI2 or PGE2 (0.1-1 microM) inhibited ISOP-induced glycerol output. Infusion of AA (0.1-1 microM) increased 6-keto-PGF1 alpha and reduced glycerol output. Infusion of sodium meclofenamate abolished the effect of AA to increase 6-keto-PGF1 alpha and to decrease glycerol output. These data suggest that prostaglandins synthesized in the heart act as an inhibitory modulator of beta-adrenergic receptor-stimulated cardiac lipolysis.

β-Adrenergic stimulation controls the expression of a thioesterase specific for very-long-chain fatty acids in perfused hearts

“…These agonists are stimulus for phospholipase A 2 and phospholipase C, both of which may provide a source of free arachidonic acid, an essential step in the generation of eicosanoids. It was also reported that badrenergic agonists stimulate arachidonic acid release in mammalian heart [8], but the mechanism by which arachidonic acid is released is not well documented.…”