PURINERGIC P2 RECEPTORS IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS ARE INVOLVED IN HYPEROSMOTIC-INDUCED SYMPATHOEXCITATION

Author(s)

Ferreira-Neto, H. C. ; Ribeiro, I. M. R. ; Moreira, T. S. ; Yao, S. T. ; Antunes, V. R.

• Document type: Journal article
• Source: Neuroscience; v. 349, p. 253-263, MAY 4 2017.
• Web of Science Citations: 1

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 (0.154 M, 0.5 mL), hypertonic saline (3 M, 0.5 mL) or hypertonic mannitol (10% w/v, 0.5 mL). 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 hyper tonic 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 pretreatment. Collectively, our findings indicate that hyperosmotic stimulation activates a subset of P2X2 expressing PVN neurons that might facilitate increased sympathetic drive. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/06206-0 - Gene expression changes of neuropeptides and proinflammatory factors of the hypothalamus and brainstem nucleus involved with cardiovascular regulation in diet-induced obesity animals
• Grantee: Vagner Roberto Antunes
• Support type: Regular Research Grants
• FAPESP's process: 10/05037-1 - Role of purinergic receptors of paraventricular nucleus of the hypothalamus in the neurogenic hypertension
• Grantee: Hildebrando Candido Ferreira Neto
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/21991-3 - Salt-induced hypertension: role of purinergic signaling in the neuronal cells at the hypothalamus level, and its correlation with the autonomic nervous system and blood pressure control
• Grantee: Vagner Roberto Antunes
• Support type: Regular Research Grants
• FAPESP's process: 10/17997-0 - Purinergic mechanisms at the hypothalamus level on sympathetic outflow and its correlation to neurogenic hypertension
• Grantee: Vagner Roberto Antunes
• Support type: Regular Research Grants