title: Purinergic P2 receptors in the paraventricular nucleus of the hypothalamus are involved in hyperosmotic-induced sympathoexcitation.
abstract: Increases in plasma osmolality activates the paraventricular nucleus of the hypothalamus (PVN) which in turn mounts a physiological response by increasing the release of arginine vasopressin and sympathetic nerve activity to end organs such as the kidney. The PVN expresses an abundance of purinergic receptors including P2X2 receptors. In the present study, we sought to determine (1) whether P2X2-expressing PVN neurons are activated by hypertonic saline or hypertonic mannitol and (2) what effects P2X receptor blockade has on sympathetic nerve activation mediated by a hyperosmotic stimulus. Male Wistar rats were randomly assigned to three groups and intravenously infused with either isotonic saline (0.154M, 0.5mL), hypertonic saline (3M, 0.5mL) or hypertonic mannitol (10% w/v, 0.5mL). Significantly greater numbers of Fos-positive cells were observed in the hypertonic saline (393±29)- and hypertonic mannitol (141±11)-infused rats compared with control, saline-treated, rats (47±2 neurons/PVN section). Furthermore, there was a significant increase in the number of activated (Fos-positive) P2X2 expressing PVN neurons in the hypertonic saline (65±7) and hypertonic mannitol (37±7)-treated rats compared with controls (16±2). Microinjection of a P2X receptor antagonist, PPADS, within the PVN significantly attenuated sympathetic nerve activation driven by a hyperosmotic stimulus. The hyperosmotically induced increase in lumbar sympathetic nerve activity was significantly blunted after PPADS pre-treatment. Collectively, our findings indicate that hyperosmotic stimulation activates a subset of P2X2 expressing PVN neurons that might facilitate increased sympathetic drive.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 Sao Paulo, SP, Brazil.
authors.forename: H C
authors.initials: HC
authors.lastname: Ferreira-Neto
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 Sao Paulo, SP, Brazil.
authors.forename: I M R
authors.initials: IM
authors.lastname: Ribeiro
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 Sao Paulo, SP, Brazil.
authors.forename: T S
authors.initials: TS
authors.lastname: Moreira
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Howard Florey Laboratories, University of Melbourne, Victoria 3010, Australia. Electronic address: song.yao@florey.edu.au.
authors.forename: S T
authors.initials: ST
authors.lastname: Yao
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 05508-000 Sao Paulo, SP, Brazil. Electronic address: antunes@icb.usp.br.
authors.forename: V R
authors.initials: VR
authors.lastname: Antunes
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
chemical_list: D018048:Receptors, Purinergic P2; D012462:Saline Solution, Hypertonic; D001127:Arginine Vasopressin
keywords: autonomic nervous system; hyperosmolality; hypertonic saline; mannitol; purinergic signaling; sympathetic activity