CCK-induced inhibition of presympathetic vasomotor neurons: dependence on subdiaphragmatic vagal afferents and central NMDA receptors in the rat.

Abstract

Systemic administration of cholecystokinin (CCK) inhibits a subpopulation of rostral ventrolateral medulla (RVLM) presympathetic vasomotor neurons. This study was designed to determine whether this effect involved subdiaphragmatic vagal afferents and/or central N-methyl-d-aspartic acid (NMDA) receptors. Recordings were made from CCK-sensitive RVLM presympathetic vasomotor neurons in halothane-anesthetized, paralyzed male Sprague-Dawley rats. The responses of the neurons to CCK (2 and 4 microg/kg iv), phenylephrine (PE; 5 microg/kg iv), and phenylbiguanide (PBG; 5 microg/kg iv) were tested before and after application of the local anesthetic lidocaine (2% wt/vol gel; 1 ml) to the subdiaphragmatic vagi at the level of the esophagus. In seven separate experiments, lidocaine markedly reduced the inhibitory effects of CCK on RVLM presympathetic neuronal discharge rate. In other experiments, the effect of systemic administration of dizocilpine (1 mg/kg iv), a noncompetitive antagonist at NMDA receptor ion channels, on the RVLM presympathetic neuronal responses to CCK, PBG, and PE was tested. In all cases (n = 6 neurons in 6 individual rats), dizocilpine inhibited the effects of CCK, PBG, and PE on RVLM presympathetic neuronal discharge. These results suggest that the effects of systemic CCK on the discharge of RVLM presympathetic neurons is mediated via an action on receptors located on subdiaphragmatic vagal afferents. Furthermore, the data suggest that CCK activates a central pathway involving NMDA receptors to produce inhibition of RVLM presympathetic neuronal discharge.