Adrenergic inhibition of endogenous acetylcholine release on postganglionic cardiac vagal nerve terminals.
OBJECTIVE
The aim was to examine the adrenergic modulation of endogenous acetylcholine (ACh) release from vagal nerve terminals in the in vivo heart.


METHODS
Using dialysis technique in anesthetized cats, we investigated the influence of exogenous noradrenaline on dialysate ACh response. Dialysis probes were implanted in the left ventricular myocardium and perfused with Krebs-Henseleit buffer containing eserine (10(-4) M) at 3 microl/min. Dialysate ACh concentration was measured as an index of ACh release from cardiac vagal nerve terminals. The dialysate ACh response to vagal nerve stimulation was examined before and after local administration of noradrenaline (10(-5) M) through dialysis probes.


RESULTS
Noradrenaline significantly attenuated the dialysate ACh response to vagal nerve stimulation (10 Hz) from 9.5+/-1.8 to 5.4+/-1.2 nM (n=7). In the presence of the alpha-adrenergic antagonist phentolamine (10(-4) M), noradrenaline did not attenuate the dialysate ACh response (from 9.8+/-2.7 to 9.4+/-2.8 nM, n=6). The N-type Ca2+ channel blocker omega-conotoxin GVIA (10(-5) M) significantly attenuated the dialysate ACh response from 9.6+/-1.2 to 4.5+/-0.7 nM (n=8). In the presence of omega-conotoxin GVIA, noradrenaline did not attenuate the dialysate ACh response (from 3.8+/-1.4 to 3.5+/-1.3 nM, n=7).


CONCLUSIONS
Our results suggest the presynaptic adrenergic inhibition of ACh release on postganglionic cardiac vagal nerve terminals. Adrenergic inhibition of Ca2+ influx through the N-type Ca2+ channels could play a predominant role in the decrease in ACh release.
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan. takiyama@ri.ncvc.go.jp
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Yamazaki
D000109:Acetylcholine / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects; D002415:Cats; D003864:Depression, Chemical; D004558:Electric Stimulation; D005260:Female; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020866:omega-Conotoxin GVIA; D000109:Acetylcholine; D009638:Norepinephrine; D010646:Phentolamine