Brain Gαi 2 -subunit proteins and the prevention of salt sensitive hypertension.
Brain Gαi 2 -subunit proteins and the prevention of salt sensitive hypertension.
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DOI：
10.3389/fphys.2015.00233
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发表时间：
2015
影响因子：
4
通讯作者：
Wainford RD
中科院分区：
文献类型：
--
作者：
Carmichael CY;Wainford RD
为了对抗盐敏感性高血压的发展，多个脑G蛋白偶联受体（GPCR）系统被激活以促进交感神经抑制、钠稳态和正常血压。目前，关于下游GPCR激活的Gα亚基蛋白在长期血压调节所需的这些至关重要的生理调节反应中的作用的知识还很少。我们已经确定，在清醒的Sprague-Dawley大鼠中，脑Gαi2蛋白介导由急性药理学（外源性中枢痛敏素/FQ受体（NOP）和α2-肾上腺素受体激活）和生理学挑战钠稳态（静脉容量扩张和1 M钠负荷）产生的利钠和交感神经抑制反应。我们已经证明，在耐盐大鼠表型中，高饮食盐摄入引起下丘脑室旁核（PVN）Gαi2蛋白的位点特异性上调。此外，我们确定PVN Gαi2蛋白上调可预防Sprague-Dawley和Dahl盐耐受大鼠肾神经依赖性交感神经介导的盐敏感性高血压的发展。此外，在高盐摄入期间未能上调PVN Gαi2蛋白有助于Dahl盐敏感性（DSS）高血压的病理生理学。总的来说，我们的数据表明，脑，可能PVN特异性，Gαi2蛋白途径代表了一个中央分子途径介导交感神经抑制肾神经依赖性反应诱发维持钠稳态和耐盐表型。此外，这种内源性“抗高血压”机制的损害有助于盐敏感性高血压的病理生理学。
To counter the development of salt-sensitive hypertension, multiple brain G-protein-coupled receptor (GPCR) systems are activated to facilitate sympathoinhibition, sodium homeostasis, and normotension. Currently there is a paucity of knowledge regarding the role of down-stream GPCR-activated Gα-subunit proteins in these critically important physiological regulatory responses required for long-term blood pressure regulation. We have determined that brain Gαi2-proteins mediate natriuretic and sympathoinhibitory responses produced by acute pharmacological (exogenous central nociceptin/orphanin FQ receptor (NOP) and α2-adrenoceptor activation) and physiological challenges to sodium homeostasis (intravenous volume expansion and 1 M sodium load) in conscious Sprague–Dawley rats. We have demonstrated that in salt-resistant rat phenotypes, high dietary salt intake evokes site-specific up-regulation of hypothalamic paraventricular nucleus (PVN) Gαi2-proteins. Further, we established that PVN Gαi2 protein up-regulation prevents the development of renal nerve-dependent sympathetically mediated salt-sensitive hypertension in Sprague–Dawley and Dahl salt-resistant rats. Additionally, failure to up-regulate PVN Gαi2 proteins during high salt-intake contributes to the pathophysiology of Dahl salt-sensitive (DSS) hypertension. Collectively, our data demonstrate that brain, and likely PVN specific, Gαi2 protein pathways represent a central molecular pathway mediating sympathoinhibitory renal-nerve dependent responses evoked to maintain sodium homeostasis and a salt-resistant phenotype. Further, impairment of this endogenous “anti-hypertensive” mechanism contributes to the pathophysiology of salt-sensitive hypertension.