A 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-urethan-anesthetized, beta-blocked rats, the cervical vagus nerve was cut and the distal cut end was electrically stimulated to induce vagal bradycardia (VIB). Sustained electrical stimulation of the dPAG attenuated VIB in a duration-dependent manner but did not affect bradycardia induced by intravenous acetyl-choline (AIB). The dPAG inhibition of VIB was abolished by C1 transection. Intravenous norepinephrine (NE) reduced VIB but did not affect AIB. Both the dPAG and NE inhibitions of VIB 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 C1 transection. Prazosin treatment did reduced the inhibition, but only moderately. In conclusion, the dPAG has a potential ability to suppress VIB 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.