Aldosterone infusion into the 4th ventricle produces sodium appetite with baroreflex attenuation independent of renal or blood pressure changes

Abstract

Aldosterone infusion into the 4th ventricle (4th V), upstream the nucleus of the solitary tract (NTS), produces strong 0.3 M NaCl intake. In the present study, we investigated whether aldosterone infusion into the 4th V activates HSD2 neurons, changes renal excretion, or alters blood pressure and cardiovascular reflexes. Chronic infusion of aldosterone (100 ng/h) into the 4th V increased daily 0.3 M NaCl intake (up to 44 ± 10, vs. vehicle: 5.6 ± 3.4 ml/24 h) and also c-Fos expression in HSD2 neurons in the NTS and in non-HSD2 neurons in the NTS. Natriuresis, diuresis and positive sodium balance were present in rats that ingested 0.3 M NaCl, however, renal excretion was not modified by 4th V aldosterone in rats that had no access to NaCl. 4th V aldosterone also reduced baroreflex sensitivity (-2.8 ± 0.5, vs. vehicle: -5.1 ± 0.9 bpm/mmHg) in animals that had sodium available, without changing blood pressure. The results suggest that sodium intake induced by aldosterone infused into the 4th V is associated with activation of NTS neurons, among them the HSD2 neurons. Aldosterone infused into the 4th V in association with sodium intake also impairs baroreflex sensitivity, without changing arterial pressure.

Central afferents to the nucleus of the solitary tract in rats and mice

“…In particular, the aldosterone‐sensitive HSD2 neurons in the medial NTS drive the craving for salt after sodium deprivation (Jarvie & Palmiter, 2017; Resch et al, 2017). They are activated by experimental conditions that stimulate sodium appetite, including dietary sodium deprivation and aldosterone infusion into the fourth ventricle (Gasparini et al, 2018; Geerling & Loewy, 2007). Beyond sodium appetite, in both rodents and humans sodium deprivation and elevated aldosterone cause adverse changes in mood, including anhedonia, fatigue, anxiety, and depression (August, Nelson, & Thorn, 1958; Bou‐Holaigah, Rowe, Kan, & Calkins, 1995; Grippo, Moffitt, Beltz, & Johnson, 2006; Hlavacova et al, 2012; Malinow & Lion, 1979; McCance, 1936; Morris, Na, Grippo, & Johnson, 2006; Reincke, 2018; Sonino et al, 2011).…”

Despite increasing aldosterone, elevated potassium is not necessary for activating aldosterone‐sensitive HSD2 neurons or sodium appetite

“…Therefore, while our results do not support a major role for potassium, low statistical power prevents us from drawing strong conclusions as to whether elevated potassium may augment HSD2 neuronal activation and sodium appetite. Some of our results, such as the low-level activation of HSD2 neurons in two potassium-supplemented rats, hint that hyperkalemia may have an effect, as might be expected from increasing aldosterone, which promotes both HSD2 neuronal activity and sodium appetite (Gasparini et al, 2018;Resch et al, 2017). Next, we used increased plasma protein as a proxy for reduced ECF volume.…”

“…These cells, referred to as HSD2 neurons and located in the nucleus of the solitary tract, drive sodium appetite (Geerling et al, 2006; Jarvie & Palmiter, 2017; Resch et al, 2017). Infusing aldosterone activates them and elicits sodium appetite in rats (Formenti et al, 2013; Gasparini et al, 2018), and destroying them reduces sodium appetite in mice (Resch et al, 2017). Importantly, however, their activation and sodium appetite still occur in adrenalectomized rats with no detectable aldosterone (Geerling, Engeland, et al, 2006; Jalowiec & Stricker, 1973; Rice & Richter, 1943).…”

“…It requires low‐sodium status detection and a coordinated drive to seek and ingest salty foods. Interestingly, this elaborate behavior can be elicited by administering a singular hormone, aldosterone (Formenti et al, 2013; Gasparini et al, 2018; Geerling & Loewy, 2008). Aldosterone is a mineralocorticoid produced in the zona glomerulosa of the adrenal cortex.…”

ANG II and Aldosterone Acting Centrally Participate in the Enhanced Sodium Intake in Water-Deprived Renovascular Hypertensive Rats

“…In addition, aldosterone, another hormone of the RAAS, acting centrally also induces sodium appetite ( Epstein, 1982 ; Sakai et al, 1986 ; Geerling et al, 2006a ), and a synergistic effect of aldosterone and ANG II acting in the central nervous system has been demonstrated for sodium intake ( Epstein, 1982 ; Sakai et al, 1986 ). The effects of aldosterone acting in the brain stem, particularly in the nucleus of the solitary tract (NTS), have been elegantly shown ( Geerling et al, 2006a ; Geerling et al, 2006b ; Geerling and Loewy, 2009 ; Gasparini et al, 2018 ).…”