Prejunctional mechanism in midbrain periaqueductal gray inhibition of vagal bradycardia in rats

Stimulation of the dorsal part of the midbrain periaqueductal gray matter (dPAG) inhibits baroreflex vagal bradycardia (BVB) via a central mechanism. Here we report that the dPAG suppresses vagal bradycardia also by a peripheral mechanism. In chloralose-urethananesthetized, beta-blocked rats, the cervical vagus nerve was cut and the distal cut end was electrically stimulated to induce vagal bradycardia (VIE). Sustained electrical stimulation of the dPAG attenuated VIE in a duration-dependent manner but did not affect bradycardia induced by intravenous acetylcholine (AIB). The dPAG inhibition of VIB was abolished by C-1 transection. Intravenous norepinephrine (NE) reduced VIE but did not affect AIB. Both the dPAG and NE inhibitions of VIE were largely attenuated during intravenous prazosin, a selective alpha(1)-receptor antagonist. In contrast, BVB provoked by aortic depressor nerve stimulation was remarkably inhibited by a shortly preceding dPAG stimulation, but this inhibition was not affected by C-1 transection. Prazosin treatment did reduced the inhibition, but only moderately. In conclusion, the dPAG has a potential ability to suppress VIE by prejunctionally inhibiting acetylcholine release from cardiac vagus nerve terminals via alpha(1)-receptors. However, dPAG stimulation first suppresses BVB largely at a central site, leaving a limited fraction of vagal outflow to be inhibited by a prejunctional mechanism operating with long latency.