Intra‐carotid hyperosmotic stimulation increases Fos staining in forebrain organum vasculosum laminae terminalis neurones that project to the hypothalamic paraventricular nucleus

Abstract

Body fluid hyperosmolality has long been known to elicit homeostatic responses that range from drinking to inhibition of salt appetite to release of neurohypohyseal hormones (i.e. vasopressin and oxytocin). More recently, it has been recognized that hyperosmolality is capable of also provoking a significant increase of sympathetic nerve activity (SNA). It has been reported that neurones in the forebrain organum vasculosum laminae terminalis (OVLT) and hypothalamic paraventricular nucleus (PVN) each contribute significantly to this response. Here we sought to determine if sympathoexcitatory levels of hyperosmolality activate specifically those OVLT neurones that form a monosynaptic pathway to the PVN. First, we established in anaesthetized rats that graded concentrations of hypertonic NaCl (1.5 and 3.0 osmol kg −1 ) elicit graded increases of renal SNA (RSNA) when infused at a rate of 0.1 ml min −1 through an internal carotid artery (ICA) -the major vascular supply of the forebrain. Next, infusions were performed in conscious rats in which OVLT neurones projecting to the PVN (OVLT-PVN) were retrogradely labelled with cholera toxin subunit B (CTB). Immunostaining of the immediate early gene product Fos and CTB was performed to quantify osmotic activation of OVLT-PVN neurones. ICA infusions of hypertonic NaCl and mannitol each significantly (P < 0.01-0.001) increased the number of Fos immunoreactive (Fos-ir) neuronal nuclei in the dorsal cap (DC) and lateral margins (LM) of OVLT. In the LM, infusions of 1.5 and 3.0 osmol kg −1 NaCl produced similar increases in the number of Fos-ir neurones. In the DC, these infusions produced graded increases in Fos expression. Among OVLT neurones with axons projecting directly to the PVN (i.e. CTB-ir), graded hypertonic NaCl infusions again produced graded increases in Fos expression and this was observed in both the DC and LM. Although the DC and LM contained a similar number of OVLT-PVN neurones, the proportion of such neurones that expressed Fos-ir in responses to ICA hypertonic NaCl infusions was greater in the DC (P < 0.001). These findings support the conclusion that PVN-projecting neurones in the DC and LM of OVLT could participate in behavioural, neuroendocrine, and sympathetic nervous system responses to body fluid hyperosmolality.

Role of the organum vasculosum of the lamina terminalis for the chronic cardiovascular effects produced by endogenous and exogenous ANG II in conscious rats

“…Importantly, it has already been demonstrated that the vasoconstrictive effects produced by stimulation of the entire AV3V region have origins in the OVLT (23) that, in turn, is activated after elevation of central osmolality (33) increasing sympathetic activity (34). Recent results in anesthetized rats (1) drinking 0.9% NaCl have suggested that neurons from forebrain areas, such as OVLT influence the excitability of the rostral ventrolateral medulla (RVLM), one of the most important areas for the cardiovascular control (17,18).…”

“…Our results suggest that like increases in central osmolality, increased plasma ANG II is sensed by the OVLT, and this activation also is important for chronic cardiovascular regulation. Also, because OVLT cells are responsive to increases in central osmolality (33,34), as well as ANG II (4,32), it is likely that the OVLT is a crucial site in the forebrain that contributes to hypertension induced by a combination of salt and ANG II, a currently well-reviewed concept in the field of neurogenic hypertension (29).…”

“…The OVLT is a CVO that houses receptors for ANG II (2,25) and is also very sensitive to increases of osmolality (33,34). Excesses of plasma sodium and increases of ANG II is a dangerous combination that can result in hypertension (29).…”

Chronic intermittent hypoxia increases sympathetic control of blood pressure: role of neuronal activity in the hypothalamic paraventricular nucleus

“…According to previous studies (54,55), hypertonic saline increases SNA and MAP through a mechanism that depends largely on neurons of the forebrain organum vasculosum laminae terminalis, which an anatomic study (19) has shown to send mostly glutamatergic projections to downstream sympathetic control regions of the PVN. It should be acknowledged that the exaggerated LSNA response to hypertonicity observed in CIHexposed rats could have arisen from the recruitment of PVNindependent sympathoexcitatory mechanisms or neural pathways.…”

“…In separate groups of sham (n ϭ 9) and CIH-exposed (n ϭ 9) rats, osmotic-sensitive regions of the forebrain were stimulated as previously described (6,54,55,58,59). Briefly, warmed (37°C) aqueous solutions of isotonic (290 mosM) and hypertonic (870 mosM) saline (NaCl) were delivered in a volume of 100 l over 10 -15 s through a flame-pulled fine-tipped catheter (PE-50 tubing) inserted into the internal carotid artery (ICA).…”