Centrally administered ghrelin activates cardiac vagal nerve in anesthetized rabbits

Abstract

Although central ghrelin has cardioprotective effect through inhibiting sympathetic nerve activity, the effects of central ghrelin on cardiac vagal nerve remain unknown. We investigated the effects of centrally administered ghrelin on cardiac autonomic nerve activities using microdialysis technique. A microdialysis probe was implanted in the right atrial wall adjacent to the sinoatrial node of an anesthetized rabbit and was perfused with Ringer's solution containing a cholinesterase inhibitor, eserine. After injection of ghrelin (1nmol) into the right lateral cerebral ventricle, norepinephrine (NE) and acetylcholine (ACh) concentrations in the dialysate samples were measured as indices of NE and ACh release from nerve endings to the sinoatrial node using high-performance liquid chromatography. Heart rate was 270±4bpm at baseline and decreased gradually after ghrelin injection to 234±9bpm (P<0.01) at 60–80min, followed by gradual recovery. Dialysate ACh concentration was 5.5±0.8nM at baseline and increased gradually after ghrelin injection to 8.8±1.2nM (P<0.01) at 60–80min; the concentration started to decrease gradually from 100 to 120min after injection reaching 5.6±0.8 nM at 160–180min. Central ghrelin did not change mean arterial pressure or dialysate NE concentration. The elevated dialysate ACh concentration declined rapidly after transection of cervical vagal nerves. These results indicate that centrally administered ghrelin activates cardiac vagal nerve.