Differential effects of intravenous hyperosmotic solutes on drinking latency and c-Fos expression in the circumventricular organs and hypothalamus of the rat

Abstract

December 28, 2006; doi:10.1152/ajpregu.00547.2006.-Hyperosmotic intravenous infusions of NaCl are more potent for inducing drinking and vasopressin (AVP) secretion than equally osmotic solutions of glucose or urea. The fact that all three solutes increased cerebrospinal fluid osmolality and sodium concentration led the investigators to conclude that critical sodium receptors or osmoreceptors for stimulating drinking and AVP secretion were outside the blood-brain barrier (BBB) in the circumventricular organs (CVOs). We tested an obvious prediction of this hypothesis: that all three solutes should increase c-Fos-like immunoreactivity (Fos-ir) inside the BBB, but that only NaCl should increase Fos-ir in the CVOs. We gave intravenous infusions of 3.0 Osm/l NaCl, glucose, or urea to rats for 11 or 22 min at 0.14 ml/min and perfused the rats for assay of Fos-ir at 90 min. Controls received isotonic NaCl at the same volume. Drinking latency was measured, but water was then removed. Drinking consistently occurred with short latency during hyperosmotic NaCl infusions only. Fos-ir in the forebrain CVOs, the subfornical organ, and organum vasculosum laminae terminalis was consistently elevated only by hyperosmotic NaCl. However, all three hyperosmotic solutes potently stimulated Fos-ir in the supraoptic and paraventricular nuclei of the hypothalamus inside the BBB. Hyperosmotic NaCl greatly elevated Fos-ir in the area postrema, but even glucose and urea caused moderate elevations that may be related to volume expansion rather than osmolality. The data provide strong support for the conclusion that the osmoreceptors controlling drinking are located in the CVOs. area postrema; c-Fos; drinking; hypernatremia; organum vasculosum laminae terminalis; osmoreceptors; paraventricular nucleus of the hypothalamus; subfornical organ; supraoptic nucleus THE BRAIN AREAS THAT CONTAIN electrophysiologically defined osmoreceptive cells that function in the regulation of fluid and electrolyte balance include the circumventricular organs (CVOs), the median preoptic nucleus (MnPO), the hypothalamic supraoptic and paraventricular nuclei (SON and PVN), and the nucleus of the solitary tract (1,17,18,33,34,40,43). These areas are intricately interconnected by neural pathways into a network subserving fluid balance as originally described by Miselis (29). Candidate mechanisms for osmoreceptors have been identified among aquaporins, the vanilloid family of transient receptor potential channels, and mechanical gating of sodium currents (3,22,44,45). However, electrophysiological studies in single neurons or brain slices do little to differentiate which osmoreceptors are more important for functions such as AVP secretion or drinking.The concept that the critical osmoreceptors for these functions are located in the CVOs and in the peripheral nervous system stems from three influential studies that demonstrated drinking in sheep, dogs, and rats was elicited by intravenous hyperosmotic NaCl or sucrose but not by urea or glucose (8,26,41). The generally...

ENaC-expressing neurons in the sensory circumventricular organs become c-Fos activated following systemic sodium changes

“…This study demonstrates that: 1) the concentration of ENaC-expressing neurons in the sensory CVOs greatly exceeds that found in nearby brain sites by ϳ2 times; 2) ENaC-expressing CVO neurons become c-Fos activated following intraperitoneal injections of hypertonic saline, while comparable injections of isotonic saline had no effect and these findings are in agreement with a previous study (22); 3) sodium deprivation induces c-Fos activation of ENaC-expressing neurons in the OVLT and SFO but has no noticeable effect in the AP; the latter result is different from what has been reported in sodium depletion experiment in which the diuretic drug furosemide was used to induce NaCl loss (35) perhaps because this drug blocks GABA-A receptors in the brain (29); 4) sodium repletion elicits c-Fos activation of ENaC-expressing neurons in all three sensory CVOs, especially in the AP; and 5) increases in c-Fos activity in the CVOs were correlated with increases plasma sodium concentration.…”

Adropin Is a Key Mediator of Hypoxia Induced Anti-Dipsogenic Effects via TRPV4-CamKK-AMPK Signaling in the Circumventricular Organs of Rats

“…Similarly, water-deprived animals have increased motivation of drinking water (Stricker and Sved, 2000; McKinley and Johnson, 2004). Previous studies found that CVOs are the closest in relation with drinking water outside the BBB, such as SFO, MnPO and OVLT, which constitute nerve fibers network and contribute to the stability of osmotic pressure (Miselis, 1981; Ho et al, 2007). As compared to high urea or sugar, high osmotic pressure easily affects the CVO neurons, and ultimately retro-regulates animal’s thirst perception and water consumption to reduce plasma osmotic pressure (Noda and Sakuta, 2013; Oka et al, 2015).…”

Organum vasculosum laminae terminalis contributes to increased sympathetic nerve activity induced by central hyperosmolality

“…The OVLT plays a major role in hyperosmolality-stimulated thirst (19,27,28,44,48) and pituitary release of vasopressin (30,44,48) and oxytocin (17,35). To date, however, involvement of OVLT in mediating hyperosmolality-induced increases of SNA has not been directly assessed.…”