Marloes C van Haaster1,2, Alicia A McDonough3, Susan B Gurley2. 1. Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. 2. Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. 3. Department of Integrative Anatomical Sciences, Los Angeles, California, USA.
Abstract
PURPOSE OF REVIEW: The renin-angiotensin system (RAS) plays a critical role in the pathogenesis of hypertension. Homeostatic actions of the RAS, such as increasing blood pressure (BP) and vasoconstriction, are mediated via type 1 (AT1) receptors for angiotensin II. All components of the RAS are present in the renal proximal tubule, which reabsorbs the bulk of the glomerular filtrate, making this segment of the nephron a location of great interest for solute handling under RAS influence. This review highlights recent studies that illustrate the key role of renal proximal tubule AT1 receptors in BP regulation. RECENT FINDINGS: A variety of investigative approaches have demonstrated that angiotensin II signaling via AT1a receptors, specifically in the renal proximal tubule, is a major regulator of BP and sodium homeostasis. Reduction of proximal tubule AT1a receptors led to lower BPs, whereas overexpression generally caused increased BPs. SUMMARY: AT1a receptors in the proximal tubule are critical to the regulation of BP by the kidney and the RAS. The pattern of BP modulation is associated with alterations in sodium transporters. As a key site for sodium homeostasis, the renal proximal tubule could hence be a potential target in the treatment of hypertension.
PURPOSE OF REVIEW: The renin-angiotensin system (RAS) plays a critical role in the pathogenesis of hypertension. Homeostatic actions of the RAS, such as increasing blood pressure (BP) and vasoconstriction, are mediated via type 1 (AT1) receptors for angiotensin II. All components of the RAS are present in the renal proximal tubule, which reabsorbs the bulk of the glomerular filtrate, making this segment of the nephron a location of great interest for solute handling under RAS influence. This review highlights recent studies that illustrate the key role of renal proximal tubule AT1 receptors in BP regulation. RECENT FINDINGS: A variety of investigative approaches have demonstrated that angiotensin II signaling via AT1a receptors, specifically in the renal proximal tubule, is a major regulator of BP and sodium homeostasis. Reduction of proximal tubule AT1a receptors led to lower BPs, whereas overexpression generally caused increased BPs. SUMMARY:AT1a receptors in the proximal tubule are critical to the regulation of BP by the kidney and the RAS. The pattern of BP modulation is associated with alterations in sodium transporters. As a key site for sodium homeostasis, the renal proximal tubule could hence be a potential target in the treatment of hypertension.
Authors: Matthew A Sparks; Emre Dilmen; Donna L Ralph; Fitra Rianto; Thien A Hoang; Alison Hollis; Edward J Diaz; Rishav Adhikari; Gabriel Chew; Enrico G Petretto; Susan B Gurley; Alicia A McDonough; Thomas M Coffman Journal: Am J Physiol Renal Physiol Date: 2021-05-10