Antagonistic Oxytocin/α₂‐Adrenoreceptor Interactions in the Nucleus Tractus Solitarii: Relevance for Central Cardiovascular Control

Abstract

The modulation of the central cardiovascular effects of alpha2-adrenoceptor activation by oxytocin in the nucleus tractus solitarii has been evaluated by cardiovascular analysis and by quantitative receptor autoradiography. Microinjections in the nucleus tractus solitarii of a threshold dose of oxytocin effectively and significantly counteracted the vasodepressor and bradycardic actions of an ED50 dose of the alpha2-adrenoceptor agonist clonidine. The coinjection of a threshold dose of oxytocin with a threshold dose of clonidine did not produce any changes in the mean arterial pressure but a tachycardic response was observed. Receptor autoradiographical experiments showed that oxytocin (3 nM) significantly increased the Kd and Bmax values of [3H]p-aminoclonidine binding sites in the nucleus tractus solitarii compatible with a possible antagonistic interaction with the alpha2-adrenoceptors, and this effect was blocked by the presence of the specific oxytocin receptor antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin. These findings suggest the existence of an antagonistic oxytocin/alpha2-adrenoceptor interaction in nucleus tractus solitarii that may be of relevance for the demonstrated modulation of alpha2-adrenoceptor induced cardiovascular responses by oxytocin.

Long‐Term Modulation By Postnatal Oxytocin of the α2‐Adrenoceptor Agonist Binding Sites in Central Autonomic Regions and the Role of Prenatal Stress

“…The increased density of α 2 ‐adrenoceptor agonist binding sites in the offpring of ad libitum treated dams were substantial in the NTS and in the hypothalamus, but absent in the amygdala. Similar effects have been observed in vitro after oxytocin incubation of brain sections in the nM range, but a reduction of α 2 ‐adrenoceptor affinity by oxytocin was the major change here (3, 4). The B max increase may reflect an increased α 2 ‐adrenoceptor density and/or an increased number of α 2 ‐adrenoceptors in the high affinity state (4).…”

In vivo evaluation of α2-adrenoceptors in cats with idiopathic cystitis

“…Heart rate is controlled, in part, by central postsynaptic α 2 -ARs in the nucleus of the solitary tract. 18 Pupil dilation occurs via stimulation of centrally located, post- Table 1-Mean ± SD percentage changes in heart rate 10 minutes after medetomidine (20 µg/kg, IM) was administered to 12 stressed healthy cats and 13 stressed cats with FIC; on days 1 through 8 cats were stressed, whereas on days 9 through 35 cats were housed in a nonstress enriched environment. synaptic α 2 -ARs located in the Edinger-Westfal nucleus.…”

α2-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

“…These alterations in baroreflex function in the SHR have been associated with a reduction in both catecholamine content in the NTS and ␣ 2 -adrenoreceptor numbers within the NTS (27,36,37). Moreover, stimulation of ␣ 2 -adrenoreceptors in normotensive rats lowers resting pressure and augments arterial baroreflex function (3,7,19,20) and blockade of these receptors significantly attenuates baroreflex control of MAP, HR, and RSNA and can raise resting pressures (19,30,35). These observations suggest that altered ␣ 2 -adrenoreceptor function within the NTS may play a role in baroreflex dysfunction in the SHR.…”