Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow

Author(s)

Ferreira-Neto, H. C. ^[1] ; Yao, S. T. ^[2] ; Antunes, V. R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic - Australia

• Document type: Journal article
• Source: PURINERGIC SIGNALLING; v. 9, n. 3, p. 337-349, SEP 2013.
• Web of Science Citations: 6

Abstract

P2X receptors are expressed on ventrolateral medulla projecting paraventricular nucleus (PVN) neurons. Here, we investigate the role of adenosine 5'-triphosphate (ATP) in modulating sympathetic nerve activity (SNA) at the level of the PVN. We used an in situ arterially perfused rat preparation to determine the effect of P2 receptor activation and the putative interaction between purinergic and glutamatergic neurotransmitter systems within the PVN on lumbar SNA (LSNA). Unilateral microinjection of ATP into the PVN induced a dose-related increase in the LSNA (1 nmol: 38 +/- 6 %, 2.5 nmol: 72 +/- 7 %, 5 nmol: 96 +/- 13 %). This increase was significantly attenuated by blockade of P2 receptors (pyridoxalphosphate-6-azophenyl-20,40-disulphonic acid, PPADS) and glutamate receptors (kynurenic acid, KYN) or a combination of both. The increase in LSNA elicited by L-glutamate microinjection into the PVN was not affected by a previous injection of PPADS. Selective blockade of non-N-methyl-D-aspartate receptors (6-cyano-7-nitroquinoxaline-2,3-dione disodium salt, CNQX), but not N-methyl-D-aspartate receptors (NMDA) receptors (DL-2-amino-5-phosphonopentanoic acid, AP5), attenuated the ATP-induced sympathoexcitatory effects at the PVN level. Taken together, our data show that purinergic neurotransmission within the PVN is involved in the control of SNA via P2 receptor activation. Moreover, we show an interaction between P2 receptors and non-NMDA glutamate receptors in the PVN suggesting that these functional interactions might be important in the regulation of sympathetic outflow. (AU)

• 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
• FAPESP's process: 07/04085-0 - Functional analysis of genes contributing to neurogenic hypertension
• 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