FASEB J：研究人员发现大脑调节肾功能的信号

近日，波士顿大学医学院（BUSM）的研究人员发现大脑中调节肾脏排泄钠的信号通路。这一发现刊登在Journal of the Federation of American Societies for Experimental Biology杂志上。

高血压或慢性血压高，影响了三分之一的成年人，能显着增加心血管疾病的风险和死亡率。高血压患者中约50％是对盐敏感的，表现为盐摄入后血压会上升。

据研究人员介绍，有关大脑为控制体内盐，通过肾脏清除体内的盐的作用机制知之甚少。助理教授Richard Wainford博士说：我们的数据表明钠摄入量的变化导致了大脑丘脑室旁核（PVN内）Gαi2蛋白水平的变化。

Wainford和他的团队探索了大脑中Gαi2信号转导蛋白调节盐和水排泄以及调控血压的作用途径。他们发现PVN内的Gαi2亚基蛋白在介导肾脏排泄钠、抑制肾交感神经传导至肾脏中的过程中起到关键作用。

这些研究结果为改善心血管和肾脏排泄功能提供了一种新方，这可能有助于治疗多种疾病状态如盐敏感高血压和钠摄入量升高引起的充血性心脏衰竭等。（生物谷：Bioon.com）

doi:10.1096/fj.11-196550
PMC:
PMID:

Brain heterotrimeric Gαi2-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress

Daniel R. Kapusta*,†, Crissey L. Pascale* and Richard D. Wainford*,¹

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 Gαi₂-subunit protein pathways mediate the natriuretic response to α₂-adrenoreceptor activation in vivo. Consequently, we examined the role of brain Gαi₂ 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 oligodeoxynucleotide (ODN)-mediated down-regulation of brain Gαi₂ 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 Gαi₂ 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 Gαi₂ proteins, animals exhibited sodium retention, global sympathoexcitation, and elevated blood pressure. Collectively, these data demonstrate that PVN Gαi₂ 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 Gαi₂-subunit protein-gated pathways mediate central sympathoinhibition to maintain fluid and electrolyte homeostasis during stress.