Brain heterotrimeric G alpha i(2)-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress

作者：Kapusta Daniel R; Pascale Crissey L; Wainford Richard D^*

来源：The FASEB Journal, 2012, 26(7): 2776-2787.

DOI：10.1096/fj.11-196550

• renal sympathetic nerve activity
• RSNA
• natriuresis
• sodium homeostasis
• blood pressure regulation
• G-protein-coupled receptors

Fluid and electrolyte homeostasis is integral to blood pressure regulation. However, the central molecular mechanisms regulating the neural control of sodium excretion remain unclear. We have demonstrated that brain G alpha i(2)-subunit protein pathways mediate the natriuretic response to alpha(2)-adrenoreceptor activation in vivo. Consequently, we examined the role of brain G alpha i(2) proteins in the neural mechanisms facilitating fluid and electrolyte homeostasis in response to acute [i.v. volume expansion (VE)] or chronic stressful stimuli (dietary sodium restriction vs. supplementation) in conscious Sprague-Dawley rats. Selective oligodeoxy-nucleotide (ODN)-mediated down-regulation of brain G alpha i(2) proteins, but not a scrambled ODN, abolished the renal sympathoinhibitory response and attenuated the natriuresis to VE. In scrambled ODN-treated rats, chronic changes in dietary sodium intake evoked an endogenous, hypothalamic paraventricular nucleus (PVN)-specific, decrease (sodium deficiency) or increase (sodium excess) in PVN G alpha i(2) proteins; plasma norepinephrine levels were inversely related to dietary sodium content. Finally, in rats treated with an ODN to prevent high salt-induced up-regulation of brain G alpha i(2) proteins, animals exhibited sodium retention, global sympathoexcitation, and elevated blood pressure. Collectively, these data demonstrate that PVN G alpha i(2) protein pathways play an endogenous role in maintaining fluid and electrolyte balance by controlling the influence the sympathetic nervous system has on the renal handling of sodium.-Kapusta, D. R., Pascale, C. L., Wainford, R. D. Brain heterotrimeric G alpha i(2)-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress. FASEB J. 26, 2776-2787 (2012). www.fasebj.org

• 出版日期2012-7