Serotonergic mechanisms of the lateral parabrachial nucleus in renal and hormonal responses to isotonic blood volume expansion

Abstract

This study investigated the involvement of serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) in the control of sodium (Na ϩ ) excretion, potassium (K ϩ ) excretion, and urinary volume in unanesthetized rats subjected to acute isotonic blood volume expansion (0.15 M NaCl, 2 ml/100 g of body wt over 1 min) or control rats. Plasma oxytocin (OT), vasopressin (VP), and atrial natriuretic peptide (ANP) levels were also determined in the same protocol. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. In rats treated with vehicle in the LPBN, blood volume expansion increased urinary volume, Na ϩ and K ϩ excretion, and also plasma ANP and OT. Bilateral injections of serotonergic receptor antagonist methysergide (1 or 4 g/200 l) into the LPBN reduced the effects of blood volume expansion on increased Na ϩ and K ϩ excretion and urinary volume, while LPBN injections of serotonergic 5-HT2a/HT2c receptor agonist, 2.5-dimetoxi-4-iodoamphetamine hydrobromide (DOI; 1 or 5 g/200 l) enhanced the effects of blood volume expansion on Na ϩ and K ϩ excretion and urinary volume. Methysergide (4 g) into the LPBN decreased the effects of blood volume expansion on plasma ANP and OT, while DOI (5 g) increased them. The present results suggest the involvement of LPBN serotonergic mechanisms in the regulation of urinary sodium, potassium and water excretion, and hormonal responses to acute isotonic blood volume expansion. serotonin; natriuresis; atrial natriuretic peptide; oxytocin; vasopressin ISOTONIC BLOOD VOLUME expansion, by reflex mechanisms, induces a series of regulatory responses, including the inhibition of the sympathetic outflow to the kidney, heart, and blood vessels, reduction of renin and vasopressin (VP) secretion, and increase in the levels of circulating atrial natriuretic peptide (ANP) and oxytocin (OT) that leads to diuresis and natriuresis (1,2,12,14,20,24,45,53).There are several reports demonstrating the correlation between natriuresis and diuresis and plasma ANP levels in response to systemic volume expansion, e.g., atrial balloon inflation, blood volume expansion, salt load, and water immersion (4,7,17,32,50,59). These responses depend on the activation of sinoaortic baroreceptors and/or cardiopulmonary receptor afferents located in the atria, lungs, great veins, and ventricles that project to the nucleus of the solitary tract (NTS) (1, 12, 22). The NTS neurons convey blood volume expansion signals and project to and excite different areas within the forebrain and hindbrain to produce neuroendocrine responses. Studies using expression of the immediate early gene c-Fos as a marker of neuronal activation have shown that, in addition to the NTS, volume-loading activates the paraventricular (PVN) and supraoptic (SON) nuclei, dorsal raphe nucleus (DRN), caudal ventrolateral medulla, locus coeruleus, and also the lateral parabrachial nucleus (LPBN) (6,20,46). The LPBN, a structure lying dorsolateral to the superior cerebellar peduncle, has been shown to play an ...

Sodium intake, brain c-Fos protein and gastric emptying in cell-dehydrated rats treated with methysergide into the lateral parabrachial nucleus

“…In contrast to results from previous works [28,44], groups of cell-dehydrated rats that received methysergide or vehicle also had similar plasma concentrations of OT and AVP. The differences between the previous and present findings could relate in part to different procedures to challenge body-fluid balance.…”

“…The differences between the previous and present findings could relate in part to different procedures to challenge body-fluid balance. Examples of different procedures are isotonic blood expansion or extracellular dehydration in previous works [28,44] in contrast to cell dehydration in the present work. Another possible difference is timing of blood collection.…”

“…The PVN in turn releases oxytocin (OT), which inhibits sodium appetite and participates in a feed-back loop involving the hindbrain to inhibit gastric motility [12,26,27]. Finally, methysergide injection into the LPBN attenuates the increase in plasma OT concentration induced by blood volume expansion, and 2.5-dimethoxy-4-iodoamphetamine hydrobromide, a 5-HT 2a/2c serotonergic receptor agonist, does the opposite [28].…”

Body Sodium Overload Modulates the Firing Rate and Fos Immunoreactivity of Serotonergic Cells of Dorsal Raphe Nucleus

“…Similarly, the 5HT agonist (5HT2A/2C, 2,5-dimethoxy-4-iodoamphetamine hydrobromide), injected into the LPBN, increased the renal and endocrine response after EVE and inhibited sodium intake induced by different experimental models [15]–[20].…”

Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis

“…More recently, it has been demonstrated that serotonergic terminals of the LPBN originating from DRN serotonergic somas also participate in the regulation of renal and hormonal responses induced by an isotonic increase in the ECF 30. Animals with electrolytic lesions of the DRN or with serotonin depletion induced by the central administration of p -chlorophenylalanine display attenuated ANP release, both under resting conditions and after extracellular volume expansion 31.…”