Medetomidine Suppresses Cardiac and Gastric Sympathetic Nerve Activities but Selectively Activates Cardiac Vagus Nerve

作者：Shimizu Shuji^*; Akiyama Tsuyoshi; Kawada Toru; Kamiya Atsunori; Turner Michael James; Yamamoto Hiromi; Shishido Toshiaki; Shirai Mikiyasu; Sugimachi Masaru

来源：Circulation Journal, 2014, 78(6): 1405-1413.

DOI：10.1253/circj.CJ-13-1456

• Acetylcholine
• alpha(2)-adrenergic agonist
• Norepinephrine
• Sympathetic nerve activity
• Vagus nerve activity

Background: To identify a pharmacological agent that can selectively activate cardiac vagus nerve for potential use in vagal activation therapy against heart failure, the effects of medetomidine on autonomic nerve activities in both the heart and stomach were examined.
Methods and Results: In anesthetized rabbits, microdialysis probes were implanted into both the right atrial and gastric walls. Dialysate acetylcholine (ACh) and norepinephrine (NE) concentrations were measured by high-performance liquid chromatography. First, the effects of 100 mu g/kg of intravenous medetomidine on vagal ACh and sympathetic NE releases were examined. Medetomidine significantly increased cardiac ACh release (4.7 +/- 1.1 to 7.8 +/- 0.9 nmol/L, P<0.05), but suppressed gastric ACh release (8.0 +/- 2.6 to 3.5 +/- 1.5 nmol/L, P<0.01). In contrast, medetomidine suppressed both cardiac and gastric NE releases. Second, the effects of medetomidine on ACh releases induced by electrical vagus nerve stimulation (VNS; 10 Hz) were examined. Electrical VNS significantly increased both cardiac (6.7 +/- 1.2 to 14.8 +/- 1.8 nmol/L, P<0.01) and gastric (3.8 +/- 0.8 to 181.3 +/- 65.6 nmol/L, P<0.01) ACh releases. Medetomidine did not alter the VNS-induced increases in ACh release.
Conclusions: Medetomidine suppresses both cardiac and gastric sympathetic nerve activities. In contrast, medetomidine activates cardiac vagus nerve but inhibits gastric vagal activity. Medetomidine might be one of the potential pharmacological agents for vagal activation therapy against heart failure without the risk of gastric adverse effects.

• 出版日期2014-6