Effects Of Prostaglandin E₁ On Endocrine Cardiac Function

Prostaglandin E₁ is an E series prostaglandin produced endogenously by eyelooxygenation of dihomo-X-linolenic acid. In the cardiovascular system. the major function of prostaglandin E₁ has been known as vasodilation and antiplalelet aggregation. Atrial natriuretie peptide (ANP) is a potent diuretic and natriuretic hormone, having renal, cardiac as well as endocrinological effects and is secreted predominantly from the atrial myoeytes. The purpose of the present study was to define the direct effect of prostaglandin E₁ on the endocrine cardiac function using isolated perfused beating rabbit atria. New Zealand White rabbits of either sex weighting about 1.6 kg were used. An isolated perfused atrial preparation was prepared by the method allowing atrial pacing and measurements of changes in atrial volume during contraction (stroke volume), pulse pressure, transmural extracellular fluid translocation. cAMP and cCiMP efflux and ANP secretion.Prostaglandin E₁ significantly increased the concentration of cGMP as well as cAMP. but had no significant effects on atrial dynamics and ANP release. The effects of prostaglandin E₁ on cAMP and cGMP production were concentration-dependent. Prosiaglandin E₁-induced increase in cGMP production showed a bell-shaped concentration-response curve. Prostaglandin E₁-stimulated cGMP production was attenuated by pretreatment with N-nitro-t-arginine methyl ester (L-NAME an inhibitor of nitric oxide synthase) or H-[1.2.4] oxadiazolo [4.3-a] quinoxalin-l-one (ODQ. an inhibitor of soluble guanylyl cyclase). Prostaglandin E₁-induced increase in cGMP efflux was blocked by pretreatment with A1123848 (a selective prostaglandin receptor EP₄ antagonist) but not by pretreatment with AI16809 (a selectiveproslaglandin recepti>r I"!': antagonist). Prostaglandin Iv> significantly increased Ihe concentration of cGMP as well as CAMP, but had no signillcanl effects on atrial dynamics and ANP release. Isoproterenol (|Vadrenergie receptor agonist) also signilleanlly increased the concentration ol cAMP. accompanied by an increase o\ atrial dynamics and a decrese of ANP secretion in a time-dependent manner.These data suggest that proslaglandin \:.\ increased cCiMP production via N()-sGC pathway by KPj receptor activation. In addition, the present study also indicated prostaglandin 1^ increased cAMP efllu\ without aHeeling atrial dynamics and ANP release.