The renin–angiotensin system (RAS) is widely recognized as one of the most important vasoactive hormonal systems in the physiological regulation of blood pressure and the development of hypertension. This recognition is derived from, and supported by, extensive molecular, cellular, genetic, and pharmacological studies on the circulating (tissue-to-tissue), paracrine (cell-to-cell), and intracrine (intracellular, mitochondrial, nuclear) RAS during last several decades. Now, it is widely accepted that circulating and local RAS may act independently or interactively, to regulate sympathetic activity, systemic and renal hemodynamics, body salt and fluid balance, and blood pressure homeostasis. However, there remains continuous debate with respect to the specific sources of intratubular and intracellular RAS in the kidney and other tissues, the relative contributions of the circulating RAS to intratubular and intracellular RAS, and the roles of intratubular compared with intracellular RAS to the normal control of blood pressure or the development of angiotensin II (ANG II)-dependent hypertension. Based on a lecture given at the recent XI International Symposium on Vasoactive Peptides held in Horizonte, Brazil, this article reviews recent studies using mouse models with global, kidney- or proximal tubule-specific overexpression (knockin) or deletion (knockout) of components of the RAS or its receptors. Although much knowledge has been gained from cell- and tissue-specific transgenic or knockout models, a unifying and integrative approach is now required to better understand how the circulating and local intratubular/intracellular RAS act independently, or with other vasoactive systems, to regulate blood pressure, cardiovascular and kidney function.
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July 2018
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The 3D structure of recombinant human deoxyribonuclease I. The N-terminal leucine shown in yellow at the top of the structure was selected for PEGylation of the protein. The amino acids shown in yellow towards the bottom of the protein are those interacting with globular actin, a potent inhibitor of human deoxyribonuclease I; for details, see pages 1439–1452.
Review Article|
July 09 2018
Intratubular and intracellular renin–angiotensin system in the kidney: a unifying perspective in blood pressure control
Xiao C. Li;
Xiao C. Li
*
1Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology, Division of Nephrology, Internal Medicine, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.
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Dongmin Zhu;
Dongmin Zhu
*
1Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology, Division of Nephrology, Internal Medicine, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.
2Guangxi Science and Technology University No. 1 Affiliate Hospital, Liuzhou, Guangxi, China
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Xiaowen Zheng;
Xiaowen Zheng
1Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology, Division of Nephrology, Internal Medicine, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.
3Department of Emergency Medicine, Second Affiliate Hospital, Guangxi Medical University, Nanning, Guangxi, China
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Jiangfeng Zhang;
Jiangfeng Zhang
1Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology, Division of Nephrology, Internal Medicine, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.
3Department of Emergency Medicine, Second Affiliate Hospital, Guangxi Medical University, Nanning, Guangxi, China
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Jia L. Zhuo
1Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology, Division of Nephrology, Internal Medicine, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Correspondence: Jia L. Zhuo ([email protected])
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Publisher: Portland Press Ltd
Received:
February 15 2018
Revision Received:
June 05 2018
Accepted:
June 13 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (13): 1383–1401.
Article history
Received:
February 15 2018
Revision Received:
June 05 2018
Accepted:
June 13 2018
Citation
Xiao C. Li, Dongmin Zhu, Xiaowen Zheng, Jiangfeng Zhang, Jia L. Zhuo; Intratubular and intracellular renin–angiotensin system in the kidney: a unifying perspective in blood pressure control. Clin Sci (Lond) 18 July 2018; 132 (13): 1383–1401. doi: https://doi.org/10.1042/CS20180121
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