Inhibition by prostaglandins of adrenergic transmission in the left ventricular myocardium of anesthetized dogs.
In the intact left ventricle of pentobarbital-anesthetized dogs, we have investigated the influence of prostaglandins on cardiac adrenergic neuroeffector events. The positive inotropic response (dP/dtmax) and the coronary sinus output of norepinephrine (NE) elicited by left cardiac sympathetic nerve stimulation as well as the contractile response produced by intracoronary injections of NE were studied before and after prostaglandin synthesis inhibition, and also before and during intracoronary infusion of PGE2 and PGI2. Cardiac sympathetic nerve stimulation (1-4 Hz) and intracoronary injections of NE (30-120 ng/kg) produced frequency- and dose-related positive inotropic effects, respectively. Administration of indomethacin (10 mg/kg i.v.) augmented the increase in left ventricular dP/dtmax elicited by left cardiac sympathetic nerve stimulation or intracoronary NE injection. In indomethacin pretreated dogs, intracoronary PGE2 (30 ng kg-1 min-1) or PGI2 (60 ng kg-1 min-1) attenuated the positive inotropic effect produced by left cardiac sympathetic nerve stimulation or intracoronary injections of NE. The increase in coronary sinus output of NE elicited by cardiac sympathetic nerve stimulation was enhanced by indomethacin and attenuated during intracoronary infusion of PGE2 and PGI2. These data suggest that prostaglandins synthesized in the heart inhibit cardiac adrenergic transmission in the left ventricle in vivo by reducing release of NE elicited by left cardiac sympathetic nerve stimulation and also by attenuating the action of the neurotransmitter at effector cells.
S M
SM
Lanier
K U
KU
Malik
D000758:Anesthesia; D000818:Animals; D015232:Dinoprostone; D004285:Dogs; D004558:Electric Stimulation; D011464:Epoprostenol / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D011453:Prostaglandins; D011458:Prostaglandins E; D011464:Epoprostenol; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin