Introduction: Thiazide diuretics have the unique characteristic of increasing renal Na+ excretion, while decreasing Ca2+ excretion. However, the molecular mechanism responsible for this thiazide-induced hypocalciuria remains unclear. The present study investigates the effect of thiazides on the expression of the proteins involved in active Ca2+ transport as well as the role of extracellular volume (ECV) status.
Methods: Hydrochlorothiazide (HCTZ), 12 mg/24 hours, was administered during 7 days to Wistar rats by osmotic minipumps. In addition, ECV contraction was either prevented by Na+ repletion or induced by a low-salt diet. Expression levels of the proteins involved in active Ca2+ transport [i.e., epithelial Ca2+ channel (TRPV5/ECaC1), calbindin-D28K, Na+/Ca2+ exchanger (NCX1)], as well as the thiazide-sensitive Na+ Cl- cotransporter (NCC) were determined by real-time quantitative polymerase chain reaction (PCR) and semiquantitative immunohistochemistry.
Results: HCTZ significantly reduced urinary Ca2+ excretion (22%+/- 5% relative to controls). Hematocrit was significantly increased, confirming ECV contraction. In addition, Na+ depletion virtually abolished Ca2+ excretion (8%+/- 1%), while Na+ repletion during HCTZ treatment prevented both ECV contraction and hypocalciuria. HCTZ significantly decreased mRNA expression of TRPV5 (71%+/- 6%), calbindin-D28K (53%+/- 6%), NCX1 (51%+/- 8%) and NCC (50%+/- 11%), regardless of ECV status or calciuresis. Immunohistochemistry revealed reduced TRPV5 (43%+/- 2%), calbindin-D28K (59%+/- 1%) and NCC (56%+/- 4%) abundance. Furthermore, during HCTZ treatment, the subset of tubules coexpressing NCC and calbindin-D28K was significantly reduced (43%+/- 5%) and a disturbed cellular localization of NCC was observed.
Conclusion: These data suggest that ECV contraction is a critical determinant of the thiazide-induced hypocalciuria, which is accompanied by a decreased expression of Ca2+ transport proteins.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1046/j.1523-1755.2003.00128.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Transcriptome and metabolome analysis of osteoblasts identifies disrupted purine metabolism and parathyroid hormone associated pathway induced by P. gingivalis infection.
Bone
January 2025
Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology/School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address:
Porphyromonas gingivalis (P. gingivalis), a major pathogenic bacterium of chronic periodontitis and central player in the onset and subsequent progression of periodontitis, can cause alveolar bone resorption. The osteoblast dysfunction induced by P.
View Article and Find Full Text PDFEffects of 8 Weeks of Moderate- or High-Volume Strength Training on Sarcoplasmic Reticulum Ca Handling in Elite Female and Male Rowers.
Scand J Med Sci Sports
January 2025
Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
While acute exercise affects sarcoplasmic reticulum (SR) function, the impact of resistance training remains unclear. The purpose of the present study was to investigate SR Ca handling plasticity in response to moderate- and high-volume strength training in elite rowers. Twenty elite male (n = 12) and female (n = 8) rowers performed three weekly strength training sessions for 8 weeks and were randomly allocated to either perform 3 sets (3-SET) or progressive increase from 5 to 10 sets (10-SET) of 10 repetitions during the training period.
View Article and Find Full Text PDFEvaluating Material Design Principles for Calcium-Ion Mobility in Intercalation Cathodes.
Chem Mater
January 2025
Department of Materials Science and Engineering, University of California, Berkeley, California 94704, United States.
Multivalent-ion batteries offer an alternative to Li-based technologies, with the potential for greater sustainability, improved safety, and higher energy density, primarily due to their rechargeable system featuring a passivating metal anode. Although a system based on the Ca/Ca couple is particularly attractive given the low electrochemical plating potential of Ca, the remaining challenge for a viable rechargeable Ca battery is to identify Ca cathodes with fast ion transport. In this work, a high-throughput computational pipeline is adapted to (1) discover novel Ca cathodes in a largely unexplored space of "empty intercalation hosts" and (2) develop material design rules for Ca-ion mobility.
View Article and Find Full Text PDFGlaucomatous retinal ganglion cells: death and protection.
Int J Ophthalmol
January 2025
Department of Ophthalmology, the Second Affiliated Hospital of Xi'an Medical University, Xi'an 710038, Shaanxi Province, China.
Glaucoma is a group of diseases characterized by progressive optic nerve degeneration, with the characteristic pathological change being death of retinal ganglion cells (RGCs), which ultimately causes visual field loss and irreversible blindness. Elevated intraocular pressure (IOP) remains the most important risk factor for glaucoma, but the exact mechanism responsible for the death of RGCs is currently unknown. Neurotrophic factor deficiency, impaired mitochondrial structure and function, disrupted axonal transport, disturbed Ca homeostasis, and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.
View Article and Find Full Text PDFMitochondrial Calcium Homeostasis and Atrial Fibrillation: Mechanisms and Therapeutic Strategies Review.
Curr Probl Cardiol
January 2025
Department of Cardiology, Lanzhou University Second Hospital, Lanzhou, China. Electronic address:
Atrial fibrillation (AF) is tightly linked to mitochondrial dysfunction, calcium (Ca²⁺) imbalance, and oxidative stress. Mitochondrial Ca²⁺ is essential for regulating metabolic enzymes, maintaining the tricarboxylic acid (TCA) cycle, supporting the electron transport chain (ETC), and producing ATP. Additionally, Ca²⁺ modulates oxidative balance by regulating antioxidant enzymes and reactive oxygen species (ROS) clearance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!