Effects of ouabain on in situ cardiac sympathetic nerve endings.
Using dialysis technique, the effects of ouabain on in situ cardiac sympathetic nerve endings were examined in anesthetized cats. Dialysis probes were implanted in the left ventricular myocardium, and the concentration of dialysate norepinephrine (NE) was used as an indicator of NE output at the cardiac sympathetic nerve ending. Locally applied ouabain dose-dependently (1, 10, 100 microM) increased dialysate NE levels. This finding suggested that ouabain causes an increase in NE efflux without any requirement for prior mobilization of NE from vesicular stores. Transection of sympathetic nerves innervating the heart, was without effect on the ouabain (100 microM)-induced increase in NE efflux. Pretreatment with a Ca2+-channel blocker, omega-conotoxin GVIA (10 microg/kg i.v.) suppressed the ouabain-induced NE efflux. These data suggested that ouabain opened N-type calcium channels coupled to NE release without centrally mediated neural transmission. Furthermore, ouabain-induced NE efflux was suppressed by pretreatment with desipramine (neuronal NE uptake inhibitor, 100 microM). Our data suggest that the two mechanisms (exocytosis and carrier-mediated outward transport), to the same extent, contributed to the amount of NE efflux evoked by ouabain in in situ cardiac sympathetic nerve endings.
Yamazaki
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Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan. yamazaki@ri.ncvc.go.jp
Akiyama
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Kawada
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T
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002415:Cats; D003714:Denervation; D003891:Desipramine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010042:Ouabain / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013233:Stellate Ganglion / Q000601:surgery; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D027981:Symporters; D014630:Vagus Nerve / Q000187:drug effects*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D002316:Cardiotonic Agents; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D050484:Norepinephrine Plasma Membrane Transport Proteins; D027981:Symporters; D010042:Ouabain; D020866:omega-Conotoxin GVIA; D000254:Sodium-Potassium-Exchanging ATPase; D003891:Desipramine; D009638:Norepinephrine