MODULATION OF BETA-ADRENERGIC RECEPTOR-STIMULATED LIPOLYSIS IN THE HEART BY PROSTAGLANDINS

The purpose of the present study was to investigate the contribution o f prostaglandins to lipolysis elicited by beta-adrenergic receptor act ivation in the heart. We have studied the effect of prostaglandin E(2) (PGE(2)), prostaglandin I-2 (PGI(2)), and their precursor arachidonic acid (AA) in the presence and absence of a cyclooxygenase inhibitor, sodium meclofenamate, on glycerol output elicited by stimulation of be ta-adrenergic receptors in the isolated rabbit heart with isoprotereno l (ISOP). Bolus injections of ISOP (475 pmol) produced a constant incr ease in glycerol and 6-ketoprostaglandin F-1 alpha (6-keto-PGF(1 alpha )) output. Infusion of sodium meclofenamate (16 mu M) reduced basal an d attenuated ISOP-induced 6-keto-PGF(1 alpha) output and enhanced glyc erol output. During inhibition of endogenous prostaglandin synthesis w ith meclofenamate, infusion of PGI(2) or PGE(2) (0.1-1 mu M) inhibited ISOP-induced glycerol output. Infusion of AA (0.1-1 mu M) increased 6 -keto-PGF(1 alpha) and reduced glycerol output. Infusion of sodium mec lofenamate abolished the effect of AA to increase 6-keto-PGF(1 alpha) and to decrease glycerol output. These data suggest that prostaglandin s synthesized in the heart act as an inhibitory modulator of p-adrener gic receptor-stimulated cardiac lipolysis.