EFFECTS OF VASOPRESSIN AND ANGIOTENSIN-II ON NEURONS IN THE RAT DORSAL MOTOR NUCLEUS OF THE VAGUS, INVITRO

1. Extracellular recordings were made from 297 spontaneously firing neurones in the dorsal motor nucleus of the vagus (DMV) in slice preparations of rat medulla oblongata. Some of the neurones recorded were identified to be vagal motoneurones by antidromic stimulation. The cells fired with a slow irregular pattern at an average rate of 1.1 +/- 0.1 spikes/s (mean +/- S.E.M.). 2. Arginine vasopressin (AVP) was applied by perfusion in 196 of the 297 cells. Most of the neurones (190/196, 97 %) were excited by 10(-6) m AVP with an increase in firing rate from the basal level of 1.1 +/- 0.1 to a maximum of 2.5 +/- 0.2 spikes/s. There was a dose-dependent relation between the concentration of AVP and the increased firing rate in all DMV neurones tested (n = 38). The threshold concentration of the peptide to produce changes in firing rate was assumed to be about 10(-10) m. The remaining six neurones were not affected by application of AVP. 3. Application of oxytocin (OXT, 10(-6) M) increased the firing rate of all thirty-eight neurones tested. The effects of AVP and OXT on all neurones examined (n = 20 and 4, respectively) still persisted after blocking the synaptic transmission in a low-Ca2+ or Ca2+-free-high-Mg2+ solution, indicating the direct action of both AVP and OXT on the postsynaptic membranes. 4. The AVP-induced excitatory responses were completely but reversibly blocked by the V1-type receptor antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylene-propionic acid), 2-(O-methyl)tyrosine]-arginine vasopressin (d(CH2)5Tyr(Me)AVP) (n = 5) and Phaa-D-Tyr(Et)Phe-Gln-Asn-Lys-Pro-Arg-NH2 (n = 6), whereas a selective and reversible OXT receptor antagonist, desGly-NH2d(CH2)5[Tyr-(Me)2Thr4]ornithine vasotocin, which suppressed the OXT-induced excitation, did not block the responses to AVP (n = 11). 5. Application of angiotensin II (AII, 10(-6) m) to 153 neurones increased the firing rates of 60 (39%) neurones. The firing rate was increased from the basal level of 1.0 +/- 0.1 to a maximum of 1.8 +/- 0.2 spikes/s (n = 60). The effect of AII was completely abolished by an AII receptor antagonist, [Sar1,Ile8]angiotensin II (n = 6). There was a dose dependence of the excitatory response on AII concentration in all of eleven neurones tested. The threshold concentration was assumed to be about 10(-9) M. The activity of 5 (3%) of 153 neurones was decreased, and the remaining 88 (58%) neurones were not affected by AII. 6. After blocking synaptic transmission with low-Ca2+-high-Mg2+ medium, ten of sixteen neurones that had been excited by application of AII in normal medium still responded to AII, and the effects were abolished in the remaining six cells. 7. Of fifty-nine cells tested with both AVP and AII applied at 10(-6) M, responses of fifty-four (92%) to AVP were excitation. Of these fifty-four, fifteen were also excited by application of AII, one was inhibited, and AII had no effect on the remaining thirty-eight (70%). 8. The excitatory responses induced by AVP were completely or partially blocked by simultaneous perfusion of AII in normal medium, which were restored by [Sar1,Ile8]AII, whereas the application of AII alone had little effect. The suppressive effect of All on the AVP-induced excitation was abolished during perfusion with Ca2+-free-high-Mg2+ solution. 9. The results suggest that both AVP and OXT modulate vagal output mainly by increasing the firing rates of DMV neurones through an action on receptors for each peptide. All also increased the activity of DMV neurones, but the number of cells excited and the increase in activity were less by All than by AVP. In addition, AII suppresses AVP-induced excitation, an effect that may be mediated by synaptic transmission.