A spinal vasopressinergic mechanism mediates hyperosmolality‐induced sympathoexcitation

Abstract

An elevation in plasma osmolality elicits a complex neurohumoral response, including an activation of the sympathetic nervous system and an increase in arterial pressure. Using a combination of in vivo and in situ rat preparations, we sought to investigate whether hypothalamic vasopressinergic spinally projecting neurones are activated during increases in plasma osmolality to elicit sympathoexcitation. Hypertonic saline (HS, I.V. bolus), which produced a physiological increase in plasma osmolality to 299 ± 1 mosmol (kg water) −1 , elicited an immediate increase in mean arterial pressure (MAP) (from 101 ± 1 to 121 ± 3 mmHg) in vivo. Pre-treatment with prazosin reversed the HS-induced pressor response to a hypotensive response (from 121 ± 3 to 68 ± 2 mmHg), indicating significant activation of the sympathetic nervous system. In an in situ arterially perfused decorticate rat preparation, hyperosmotic perfusate consisted of either 135 mM NaCl, or a non-NaCl osmolyte, mannitol (0.5%); both increased lumbar sympathetic nerve activity (LSNA) by 32 ± 5% (NaCl) and 21 ± 1% (mannitol), which was attenuated after precollicular transection (7 ± 3% and 1 ± 1%, respectively). Remaining experiments used the NaCl hyperosmotic stimulus. In separate preparations the hyperosmotic-induced sympathoexcitation (21 ± 2%) was also significantly attenuated after transection of the circumventricular organs (2 ± 1%). Either isoguvacine (a GABA A receptor agonist) or kynurenic acid (a non-selective ionotropic glutamate receptor antagonist) microinjected bilaterally into the paraventricular nucleus (PVN) attenuated the increase in LSNA induced by the hyperosmotic stimulus (control: 25 ± 2%; after isoguvacine: 7 ± 2%; after kynurenic: 8 ± 3%). Intrathecal injection of a V 1a receptor antagonist also reduced the increase in LSNA elicited by the hyperosmotic stimulus (control: 29 ± 6%; after blocker: 4 ± 1%). These results suggest that a physiological hyperosmotic stimulus produces sympathetically mediated hypertension in conscious rats. These data are substantiated by the in situ decorticate preparation in which sympathoexcitation was also evoked by comparable hyperosmotic stimulation. Our findings demonstrate the importance of vasopressin acting on spinal V 1a receptors for mediating sympathoexcitatory response to acute salt loading.

ATP stimulates rat hypothalamic sympathetic neurons by enhancing AMPA receptor-mediated currents

“…Taken together, our results support a functionally relevant P2-AMPA receptor cross talk in PVN-RVLM neurons, which contributes to ATP-mediated excitatory effects on PVN sympathetic neurons. Moreover, our studies indicate that the P2-AMPA receptor coupling is engaged during an osmotic challenge, being thus a potential mechanism contributing to increased PVN neuronal activation and the enhanced sympathoexcitation evoked during this physiological challenge (Antunes et al 2006;Stocker and Toney 2005).…”

“…Previous studies have shown that acute osmotic stimulation by intravenous hypertonic saline or mannitol solution induces a PVN-dependent sympathoexcitatory response (Antunes et al 2006;Badoer et al 2003;Chen and Toney 2001;Son et al 2013;Stocker and Toney 2005). Thus, on the basis of results outlined above, we addressed whether an osmotic challenge (aCSF containing mannitol 1%, 1 min) could engage a purinergic-AMPA receptor cross talk in PVN sympathetic neurons.…”

Transcription Factor Expression in the Hypothalamo-Neurohypophyseal System of the Dehydrated Rat: Upregulation of Gonadotrophin Inducible Transcription Factor 1 mRNA Is Mediated by cAMP-Dependent Protein Kinase A

“…The PVN parvocellular division is an important integrative structure that regulates coordinated responses to perturbations in cardiovascular homeostasis, such as dehydration. Through descending projections from parvocellular neurons to the brainstem and spinal cord (Sawchenko and Swanson, 1982), the PVN directly regulates changes in sympathetic nerve activity involved in blood pressure and blood volume regulation (Toney et al, 2003;Antunes et al, 2006). The role of these novel PVN transcription factors in the coordinated cardiovascular response to an osmotic stimulus will be a focus of future studies.…”

Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats

“…The experiment involving the co-infusion of phenylephrine was repeated, in rats pre-treated with prazosin, to investigate if prazosin (a α 1 adrenergic receptor antagonist) will give answers to questions that were not answered above. The dose of prazosin (1 mg/kg) used in this study, has been previously used by other researchers (Nagai et al, 2003;Dabire, 2004;Antunes et al, 2006;Wang et al, 2006;Braga et al, 2008;PintÉRovÁ et al, 2009;Wong et al, 2011) …”

“…Dilutions below and above the doses used in literature were tested to obtain the lowest dose that produced an effect on BP and /or HR, as well as the maximum effect, which was not lethal in the SHR used in the study. The animals were The doses of losartan (30 mg/kg) (Wong et al, 1990;Choi et al, 2009a;Susic et al, 2009b), and prazosin (1 mg/kg) (Nagai et al, 2003;Dabire, 2004;Antunes et al, 2006;Wang et al, 2006;Braga et al, 2008;PintÉRovÁ et al, 2009) were obtained from literature.…”