Review
Biochemistry & Molecular Biology
Robert M. Carey, Helmy M. Siragy, John J. Gildea, Susanna R. Keller
Summary: Angiotensin II (Ang II) type-2 receptors (AT(2)R) in the kidney play a crucial role in opposing renal sodium retention induced by Ang II stimulation of Ang II type-1 receptors (AT(1)R). AT(2)Rs induce natriuresis through the activation of bradykinin, nitric oxide, and cyclic GMP signaling cascade. Defects in AT(2)R activation and protein phosphatase 2A (PP2A) in spontaneously hypertensive rats are associated with primary hypertension.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Peripheral Vascular Disease
Xiao Chun Li, Ana Paula Oliveira Leite, Xiaowen Zheng, Chunling Zhao, Xu Chen, Liang Zhang, Xinchun Zhou, Isabelle Rubera, Michel Tauc, Jia Long Zhuo
Summary: The study reveals the critical role of intratubular Ang II/AT(1) (AT(1a))/NHE3 pathways in the proximal tubules in normal blood pressure control and the development of Ang II-induced hypertension.
Review
Endocrinology & Metabolism
Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung
Summary: SGLT2 inhibitors have renal protective effects beyond glucose-lowering, although the exact mechanisms are unclear. They may involve inhibition of renal sodium and glucose reabsorption, recovery of glomerular filtration, as well as metabolism reprogramming and modulation of hypoxia, inflammation, and oxidative stress.
ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Pediatrics
Daniel N. Roberts, Paula Vallen, Maria Cronhjort, Tobias Alfven, Gabriel Sandblom, Susanna Tonroth-Horsefield, Boye L. Jensen, Per-Arne Lonnqvist, Robert Frithiof, Mattias Carlstrom, Rafael T. Krmar
Summary: This study aimed to assess the post-operative plasma-sodium concentration in children with acute appendicitis and provide a physiological explanation for plasma-sodium levels over time. The findings suggest that the use of moderately hypotonic fluid therapy after correction of extracellular fluid deficit is not necessarily associated with post-operative hyponatremia.
PEDIATRIC RESEARCH
(2023)
Article
Physiology
Alissa A. Frame, Kayla M. Nist, Kiyoung Kim, Jill T. Kuwabara, Richard D. Wainford
Summary: This study suggests that the renal sympathetic nerves, mediated by the alpha(1)-adrenoceptors, play a critical role in the natriuretic and sympathoinhibitory responses to acute increases in total body sodium, independent of blood pressure.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Peripheral Vascular Disease
Kouichi Tamura, Kengo Azushima, Sho Kinguchi, Hiromichi Wakui, Takahiro Yamaji
Summary: ATRAP is a protein that promotes AT1R internalization to inhibit its pathological activation; ATRAP is abundantly expressed in the kidney and plays a key role in regulating renal sodium handling and blood pressure modulation.
HYPERTENSION RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Brandon A. Kemp, Nancy L. Howell, John J. Gildea, Josh D. Hinkle, Jeffrey Shabanowitz, Donald F. Hunt, Mark R. Conaway, Susanna R. Keller, Robert M. Carey
Summary: It has been found that extracellular guanosine cyclic 3',5'-monophosphate (cGMP) inhibits sodium reabsorption in renal proximal tubules by activating the Src kinase. The exact target through which cGMP induces natriuresis is still unknown, but it is hypothesized that cGMP binds to the alpha 1-subunit of sodium-potassium ATPase (NKA) on the basolateral membranes of renal proximal tubules to inhibit sodium transport.
CIRCULATION RESEARCH
(2023)
Article
Medicine, Research & Experimental
Syed J. Khundmiri, Carolyn M. Ecelbarger, Joycemary Amponsem, Hong Ji, Kathryn Sandberg, Dexter L. Lee
Summary: This research found that deletion of the PPAR-alpha gene leads to an increase in blood pressure in mice, with significantly higher NKA activity and protein expression in PPAR-alpha KO mice compared to WT mice. Angiotensin II further increased the expression and activity of NKA and aquaporin 1 in both genotypes. Angiotensin II decreased the expression of several important proteins in the renal cortex of both WT and PPAR-alpha KO mice, with a more significant reduction in NCC in PPAR-alpha KO mice.
Article
Peripheral Vascular Disease
Richard A. Preston, David Afshartous, Evelyn Caizapanta, Barry J. Materson, Rolando Rodco, Eileen Alonso, Alberto B. Alonso
Summary: Steady-state sodium intake is the key determinant of potassium-induced natriuresis, with sodium excretion being low during low sodium intake and increasing sharply during high sodium intake. Sodium-sensitivity and NCC activity do not significantly impact potassium-induced natriuresis.
Article
Urology & Nephrology
Daniel E. Leisman, Tiago D. Fernandes, Vanesa Bijol, Mabel N. Abraham, Jake R. Lehman, Matthew D. Taylor, Christine Capone, Omar Yaipan, Rinaldo Bellomo, Clifford S. Deutschman
Summary: The study found that sepsis reduces the expression of renal angiotensin II receptors, leading to changes in kidney blood flow and creatinine levels. Both mouse models and clinical observations suggest that angiotensin II prevents these functional changes, while AT1R blockade exacerbates them.
KIDNEY INTERNATIONAL
(2021)
Review
Pharmacology & Pharmacy
Saeed Alshahrani
Summary: Chronic kidney disease is a complex condition with various underlying causes. Current pharmacotherapeutic treatment options aim to slow disease progression and improve quality of life but cannot achieve complete cure. The first-line treatment for controlling blood pressure in chronic kidney disease is the use of renin-angiotensin-aldosterone system modulators. These modulators, including direct renin inhibitors, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers, have different structures and mechanisms of action, leading to varying treatment outcomes. The choice of modulator depends on patient presentation, comorbidities, treatment availability and affordability, and healthcare provider expertise. Comparative studies between these modulators are currently lacking, which could provide valuable information for healthcare providers and researchers. This review compares the direct renin inhibitor (aliskiren) with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, aiming to identify specific areas of interest for intervention and the best possible treatment option.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Nutrition & Dietetics
Antonio Bernal, Maria A. Zafra, Maria J. Simon, Javier Mahia
Summary: Body sodium levels must be maintained within a narrow range to ensure proper functioning of the organism. This balance involves the delicate equilibrium between sodium intake and excretion, and is regulated through various neural and humoral pathways. Chemical messengers, such as aldosterone and angiotensin II, coordinate peripheral and central effects to maintain sodium homeostasis.
Article
Pharmacology & Pharmacy
Shao-Yu Yang, Tao-Min Huang, Tai-Shuan Lai, Nai-Kuan Chou, Chun-Hao Tsao, Yi-Ping Huang, Shuei-Liong Lin, Yung-Ming Chen, Vin-Cent Wu
Summary: The study found that preoperative use of ARBs was associated with a reduced risk of postoperative AKI, especially in high doses, while preoperative use of ACEIs or ARBs was both linked to reduced mortality and did not increase the risk of hyperkalemia.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Peripheral Vascular Disease
Gaizun Hu, Qing Zhu, Weili Wang, Dengpiao Xie, Chaoling Chen, Pin-Lan Li, Joseph K. Ritter, Ningjun Li
Summary: The study shows that the CD-S1PR1 pathway is crucial for sodium excretion and its deletion leads to sodium retention and exacerbates the development of salt-sensitive hypertension.
JOURNAL OF HYPERTENSION
(2021)
Article
Urology & Nephrology
Roemer J. Janse, Edouard L. Fu, Catherine M. Clase, Laurie Tomlinson, Bengt Lindholm, Merel van Diepen, Friedo W. Dekker, Juan-Jesus Carrero
Summary: Stopping RASi use after acute kidney injury is associated with similar risk of recurrent AKI but higher risk of death, myocardial infarction, and stroke.
CLINICAL KIDNEY JOURNAL
(2022)