In vivo assessment of acetylcholine-releasing function at cardiac vagal nerve terminals.
We examined whether the ACh concentration measured by cardiac microdialysis provided information on left ventricular ACh levels under a variety of vagal stimulatory and modulatory conditions in anesthetized cats. Local administration of KCl (n = 5) and ouabain (n = 7) significantly increased the ACh concentration in the dialysate to 4.3 +/- 0.8 and 7.3 +/- 1.3 nmol/l, respectively, from the baseline value of 0.6 +/- 0.5 nmol/l. Intravenous administration of phenylbiguanide (n = 5) and phenylephrine (n = 6) significantly increased the ACh concentration to 5.4 +/- 0.9 and 6.0 +/- 1.5 nmol/l, respectively, suggesting that the Bezold-Jarisch and arterial baroreceptor reflexes affected myocardial ACh levels. Modulation of vagal nerve terminal function by local administration of tetrodotoxin (n = 6), hemicholinium-3 (n = 6), and vesamicol (n = 5) significantly suppressed the electrical stimulation-induced ACh release from 20.4 +/- 3.9 to 0.6 +/- 0.1, 7.2 +/- 1.9, and 2.7 +/- 0.6 nmol/l, respectively. Increasing the heart rate from 120 to 200 beats/min significantly reduced the myocardial ACh levels during electrical vagal stimulation, suggesting a heart rate-dependent washout of ACh. We conclude that ACh concentration measured by cardiac microdialysis provides information regarding ACh release and disposition under a variety of pathophysiological conditions in vivo.
Kawada
T
T
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan. torukawa@res.ncvc.go.jp
Yamazaki
T
T
Akiyama
T
T
Shishido
T
T
Inagaki
M
M
Uemura
K
K
Miyamoto
T
T
Sugimachi
M
M
Takaki
H
H
Sunagawa
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D002415:Cats; D006329:Heart Conduction System / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles; D006426:Hemicholinium 3 / Q000494:pharmacology; D017551:Microdialysis; D009206:Myocardium / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*
D001645:Biguanides; D010880:Piperidines; D010656:Phenylephrine; D006426:Hemicholinium 3; C006189:vesamicol; D013779:Tetrodotoxin; D011189:Potassium Chloride; D000109:Acetylcholine; D011188:Potassium; C008846:phenyl biguanide