Prostacyclin as neuromodulator in the sympathetically stimulated rabbit heart.
Prostaglandin E2 (PGE2) has previously been shown to inhibit sympathetic neurotransmission in different organs and species. Based on this inhibitory effect and on its reversal by cyclo-oxygenase inhibitors, PGE2 has been claimed to be a physiological modulator of in vivo release of norepinephrine (NE) from sympathetic nerves. It is now recognized that prostacyclin (PGI2) is the main cyclo-oxygenase product in the heart. We therefore addressed the question whether PGI2, within the same preparation, is formed in increased amounts during sympathetic nerve stimulation and has neuromodulatory activity. The effluent from isolated rabbit hearts subjected to sympathetic nerve stimulation or to infusion of NE or adenosine (ADO) was collected, and its content of PGE2 and 6-keto-PGF1 alpha (dehydration product of PGI2) was analyzed using gas chromatography/mass spectrometry, operated in the negative ion/chemical ionization mode. Other hearts were infused with PGI2 and nerve stimulation induced outflow of endogenous NE into the effluent was analyzed using HPLC with electrochemical detection. Nerve stimulation at 5 or 10 Hz (before but not after adrenergic receptor blockade), as well as infusion of NE (10(-6)-10(-5)M) or ADO (10(-4)M) increased the cardiac outflow of 6-keto-PGF1 alpha. Basal and nerve stimulation induced efflux of 6-keto-PGF1 alpha was approximately 5 times higher than the corresponding efflux of PGE2. PGI2 dose-dependently inhibited the outflow of NE from sympathetically stimulated hearts, the inhibition at 10(-6)M being approximately 40%. On the basis of these observations we propose that PGI2 is a more likely candidate than PGE2 as a potential modulator of neurotransmission in cardiac tissue in vivo.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D015232:Dinoprostone; D004558:Electric Stimulation; D011464:Epoprostenol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D018377:Neurotransmitter Agents; D009638:Norepinephrine / Q000494:pharmacology*; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000502:physiology*
D018377:Neurotransmitter Agents; D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000241:Adenosine; D015232:Dinoprostone; D009638:Norepinephrine