In vivo assessment of acetylcholine-releasing function at cardiac vagal nerve terminals

Abstract

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.