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Review ArticleReview Article

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

Hiroyuki Kobori, Masaomi Nangaku, L. Gabriel Navar and Akira Nishiyama
Pharmacological Reviews September 2007, 59 (3) 251-287; DOI: https://doi.org/10.1124/pr.59.3.3
Hiroyuki Kobori
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana (H.K., L.G.N., A.N.); Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan (M.N.); and Department of Pharmacology and Hypertension and Kidney Disease Research Center, Kagawa University Medical School, Kagawa, Japan (A.N.)
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Masaomi Nangaku
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana (H.K., L.G.N., A.N.); Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan (M.N.); and Department of Pharmacology and Hypertension and Kidney Disease Research Center, Kagawa University Medical School, Kagawa, Japan (A.N.)
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L. Gabriel Navar
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana (H.K., L.G.N., A.N.); Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan (M.N.); and Department of Pharmacology and Hypertension and Kidney Disease Research Center, Kagawa University Medical School, Kagawa, Japan (A.N.)
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Akira Nishiyama
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana (H.K., L.G.N., A.N.); Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan (M.N.); and Department of Pharmacology and Hypertension and Kidney Disease Research Center, Kagawa University Medical School, Kagawa, Japan (A.N.)
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Abstract

In recent years, the focus of interest on the role of the renin-angiotensin system (RAS) in the pathophysiology of hypertension and organ injury has changed to a major emphasis on the role of the local RAS in specific tissues. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by independent multiple mechanisms. Proximal tubular angiotensinogen, collecting duct renin, and tubular angiotensin II type 1 (AT1) receptors are positively augmented by intrarenal Ang II. In addition to the classic RAS pathways, prorenin receptors and chymase are also involved in local Ang II formation in the kidney. Moreover, circulating Ang II is actively internalized into proximal tubular cells by AT1 receptor-dependent mechanisms. Consequently, Ang II is compartmentalized in the renal interstitial fluid and the proximal tubular compartments with much higher concentrations than those existing in the circulation. Recent evidence has also revealed that inappropriate activation of the intrarenal RAS is an important contributor to the pathogenesis of hypertension and renal injury. Thus, it is necessary to understand the mechanisms responsible for independent regulation of the intrarenal RAS. In this review, we will briefly summarize our current understanding of independent regulation of the intrarenal RAS and discuss how inappropriate activation of this system contributes to the development and maintenance of hypertension and renal injury. We will also discuss the impact of antihypertensive agents in preventing the progressive increases in the intrarenal RAS during the development of hypertension and renal injury.

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Pharmacological Reviews: 59 (3)
Pharmacological Reviews
Vol. 59, Issue 3
1 Sep 2007
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Review ArticleReview Article

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

Hiroyuki Kobori, Masaomi Nangaku, L. Gabriel Navar and Akira Nishiyama
Pharmacological Reviews September 1, 2007, 59 (3) 251-287; DOI: https://doi.org/10.1124/pr.59.3.3

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Review ArticleReview Article

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

Hiroyuki Kobori, Masaomi Nangaku, L. Gabriel Navar and Akira Nishiyama
Pharmacological Reviews September 1, 2007, 59 (3) 251-287; DOI: https://doi.org/10.1124/pr.59.3.3
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  • Article
    • Abstract
    • I. Introduction
    • II. Physiological Actions of Angiotensin II in the Kidney
    • III. Regulation of Circulating Renin-Angiotensin System—Classic Renin-Angiotensin System Pathways
    • IV. Mechanisms Responsible for Independent Regulation of Intrarenal Renin-Angiotensin System
    • V. Augmentation of the Intrarenal Renin-Angiotensin System during Progression of Hypertension and Renal Injury
    • VI. Effects of Pharmacological Intervention with Antihypertensive Agents on the Intrarenal Renin-Angiotensin System
    • VII. Conclusions
    • Acknowledgments
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