Cyanide intoxication induced exocytotic epinephrine release in rabbit myocardium.
Cyanide intoxication, which has been used as a model of energy depletion at cardiac sympathetic nerve terminals, causes non-exocytotic release of norepinephrine (NE). However, the effect of cyanide intoxication on cardiac epinephrine (Epi) release remains unknown. Using cardiac microdialysis in the rabbit, we measured dialysate Epi and NE concentrations as indices of myocardial interstitial Epi and NE levels, respectively. Local administration of sodium cyanide (30 mM) through the dialysis probe increased both Epi and NE levels (from 11.3+/-2.3 to 32.3+/-4.4 pg/ml and from 33.6+/-6.1 to 389.0+/-71.8 pg/ml, respectively, mean+/-S.E., P<0.01). Local desipramine (100 microM) administration suppressed the cyanide induced NE response without affecting the Epi response. In contrast, local omega-conotoxin GVIA (10 microM) administration partially suppressed the cyanide induced NE response and totally abolished the Epi response. In conclusion, cyanide intoxication causes N-type Ca(2+) channel dependent exocytotic Epi release as well as inducing N-type Ca(2+) channel independent non-exocytotic NE release.
Kawada
T
T
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, Japan. torukawa@res.go.jp
Yamazaki
T
T
Akiyama
T
T
Sato
T
T
Shishido
T
T
Inagaki
M
M
Tatewaki
T
T
Yanagiya
Y
Y
Sugimachi
M
M
Sunagawa
K
K
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D017551:Microdialysis; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011817:Rabbits; D012966:Sodium Cyanide / Q000008:administration & dosage / Q000633:toxicity*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020866:omega-Conotoxin GVIA; D012966:Sodium Cyanide; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine