Functional interactions between angiotensin II and substance P in the dorsal medulla.

Abstract

be located presynaptically on SP-containing vagal afferent fibers, whereas SP binding sites are likely to be associated with intrinsic medial NTS cells. Moreover, recent studies 9 -11 reveal that SP has cardiovascular actions within the NTS, because femtomole injections of SP into this brain region produce hypotension and bradycardia similar to that elicited by Ang II. The mechanisms of neurotransmission and receptor interactions accounting for the similar actions of Ang II and SP in the NTS are not understood. However, the findings described above suggest that Ang II might cause the release of SP from vagal afferent fibers. We have used two approaches to test this possibility. First, we compared the effects of Ang II and SP on the spontaneous activity of medial NTS neurons recorded in vitro from slices of the rat dorsal medulla. Second, we determined whether Ang II stimulated the release of SP from rat medulla slices. Methods In Vitro Recording StudiesSprague-Dawley rats (250-275 g; Harlan Sprague Dawley, Inc., Indianapolis, Ind.) were anesthetized with halothane and decapitated. The dorsal medulla

Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons

“…1). These findings agree with previous reports that between one-third and onehalf of the neurons in the dorsal medial nTS region of the dog and rat are responsive to ANG II (12)(13)(14). Responsive neurons showed increases in EPSP amplitude ranging from 20% to Ͼ200% after application of the peptide ( Figs.…”

“…Twenty-six of these neurons (41%) were excited by ANG II. As in our previous studies (12,15,16,77), ANG II did not inhibit activity in any recorded cell. Responsiveness to ANG II was not related to the depth of the neuron within the slice: the 26 cells activated by ANG II were located an average of 53 Ϯ 4 m below the surface compared with the 38 neurons that did not respond to ANG II located 52 Ϯ 2 m below the surface (t ϭ 0.84, P ϭ 0.44).…”

“…Group B cells were divided into two subgroups on the basis of their responsiveness to Glu: eight cells were excited by Glu as well as by ANG II and SP, and the other six neurons were responsive only to ANG II and SP. About 75% of the 26 ANG-responsive neurons were excited by Glu, as reported previously (12).…”

“…Because the distributions of receptors for ANG II and SP are strikingly overlapped in the nTS (1,31,50), these peptides may act on a common subset of nTS neurons. Indeed, extracellular recordings suggest that many neurons in the dorsal medial nTS region that respond to ANG II are also excited by L-glutamate (Glu) and/or SP (12,77). However, SP endogenous to the nTS and microinjection of SP into the dorsal medial nTS region appear to enhance the sensitivity of the baroreceptor reflex (23,27), in contrast to the baroreflex inhibition attributed to ANG II.…”

Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii – a microinjection study in the rat

“…In this context there is an intimate relationship between glutamate and substance P at the level of NTS (Hall et al 1993). Moreover, release of substance P by ANGII was reported earlier from an in vitro slice preparation containing the NTS (Barnes et al 1991;Diz & Pirro, 1992). However, a vagally mediated bradycardia evoked by an NTS microinjection of substance P (Hall et al 1989) or a selective NK1 receptor agonist (Feldman, 1995) was not associated with changes in the sensitivity of the baroreceptor reflex.…”