Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, NC 27710, USA.
J Am Soc Nephrol. 2010 Nov;21(11):1847-51. doi: 10.1681/ASN.2009121306. Epub 2010 Sep 16.
G protein-coupled receptors (GPCRs) have key roles in cardiovascular regulation and are important targets for the treatment of hypertension. GTPase-activating proteins, such as RGS2, modulate downstream signaling by GPCRs. RGS2 displays regulatory selectivity for the Gαq subclass of G proteins, and mice lacking RGS2 develop hypertension through incompletely understood mechanisms. Using total body RGS2-deficient mice, we used a kidney crosstransplantation strategy to examine separately the contributions of RGS2 actions in the kidney from those in extrarenal tissues with regard to BP regulation. Loss of renal RGS2 was sufficient to cause hypertension, whereas the absence of RGS2 from all extrarenal tissues including the peripheral vasculature did not significantly alter BP. Accordingly, these results suggest that RGS2 acts within the kidney to modulate BP and prevent hypertension. These data support a critical role for the renal epithelium and/or vasculature as the final determinants of the intra-arterial pressure in hypertension.
G 蛋白偶联受体 (GPCRs) 在心血管调节中发挥着关键作用，是治疗高血压的重要靶点。G 蛋白激活蛋白（如 RGS2）通过 GPCR 调节下游信号转导。RGS2 对 Gαq 亚类 G 蛋白显示出调节选择性，而缺乏 RGS2 的小鼠通过尚未完全阐明的机制发展为高血压。使用全身 RGS2 缺陷型小鼠，我们使用肾脏交叉移植策略来分别研究 RGS2 在肾脏中的作用以及在肾脏以外的组织（包括外周血管）中的作用对血压调节的影响。肾脏中缺乏 RGS2 足以引起高血压，而外周血管等所有肾脏以外组织中缺乏 RGS2 并不显著改变血压。因此，这些结果表明，RGS2 在肾脏中发挥作用以调节血压并预防高血压。这些数据支持肾脏上皮细胞和/或血管作为高血压时动脉内压的最终决定因素的关键作用。
