The Role of the Hypothalamic Paraventricular Nucleus and the Organum Vasculosum Lateral Terminalis in the Control of Sodium Appetite in Male Rats

Abstract

Angiotensin II (AngII) and aldosterone cooperate centrally to produce a robust sodium appetite. The intracellular signaling and circuitry that underlie this interaction remain unspecified. Male rats pretreated with both deoxycorticosterone (DOC; a synthetic precursor of aldosterone) and central AngII exhibited a marked sodium intake, as classically described. Disruption of inositol trisphosphate signaling, but not extracellular-regulated receptor kinase 1 and 2 signaling, prevented the cooperativity of DOC and AngII on sodium intake. The pattern of expression of the immediate early gene product cFos was used to identify key brain regions that may underlie this behavior. In the paraventricular nuclei (PVN) of the hypothalamus, DOC pretreatment diminished both AngII-induced cFos induction and neurosecretion of oxytocin, a peptide expressed in the PVN. Conversely, in the organum vasculosum lateral terminalis (OVLT), DOC pretreatment augmented cFos expression. Immunohistochemistry identified a substantial presence of oxytocin fibers in the OVLT. In addition, when action potentials in the PVN were inhibited with intraparenchymal lidocaine, AngII-induced sodium ingestion was exaggerated. Intriguingly, this treatment also increased the number of neurons in the OVLT expressing AngII-induced cFos. Collectively, these results suggest that the behavioral cooperativity between DOC and AngII involves the alleviation of an inhibitory oxytocin signal, possibly relayed directly from the PVN to the OVLT.

Differential effects of mineralocorticoid and angiotensin II on incentive and mesolimbic activity

“…The hormone regimen used in the present study was previously demonstrated to increase sodium ingestion in the Veh/AngII and DOC/AngII groups and to significantly water intake in the Veh/AngII condition (Grafe et al, 2014). Here, the progressive ratio operant task was used to compare the effort rats are willing to exert for sodium ingestion after these hormone treatments.…”

“…In contrast, humoral AngII acts initially on AngII type 1 (AT1) receptors in circumventricular organs, such as the subfornical organ and the organ vasculosum of the lateral terminalis (Lind et al, 1985; McKinley et al, 1992b; Tanaka et al, 1986; Weiss and Hatton, 1990). Mineralocorticoids exert minor up-regulation of AT1 receptor levels and AT1 signaling (Grafe et al, 2014; Shelat et al, 1999a; Shelat et al, 1998; Shelat et al, 1999b). As a parallel mechanism, mineralocorticoids may exert a cooperative behavioral effect with AngII by acting elsewhere in a broader circuit.…”

“…As a parallel mechanism, mineralocorticoids may exert a cooperative behavioral effect with AngII by acting elsewhere in a broader circuit. For example, mineralocorticoids appear to remove an inhibitory influence on sodium appetite, namely oxytocin activity in the PVN (Blackburn et al, 1992; Grafe et al, 2014; Roesch et al, 2001; Stricker and Verbalis, 1987). …”

“…The treatment groups will be referred to as follows: Veh/Veh, DOC/Veh, Veh/AngII, DOC/AngII. Using this experimental design and identical doses, the DOC/AngII treatment has been shown to elicit a greater than additive effect on sodium intake, but not water intake (Grafe et al, 2014). …”

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

“…While lesion of just the SFO does not affect the DOCAsalt increase in blood pressure, fluid intake, or sodium appetite, genetic ablation of AT 1A R from the SFO attenuates DOCA-salt hypertension and polydipsia (52,103). Thus these and other data support a functional synergism between ANG II and aldosterone (42,148,149). These studies also highlight the importance of the SFO and its target nuclei to mediate central ANG II effects through AT 1 R.…”