Local and downstream actions of proximal tubule angiotensin II signaling on Na+ transporters in the mouse nephron
| Autor: | Alicia A. McDonough, Kenneth E. Bernstein, Susan B. Gurley, Zhidan Xiang, Jorge F. Giani, Jonathan W. Nelson, Joshua A. Robertson, Donna L. Ralph |
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| Rok vydání: | 2021 |
| Předmět: |
Angiotensin receptor
Sodium-Hydrogen Exchangers urogenital system Physiology Reabsorption Chemistry Angiotensin II Membrane Transport Proteins Natriuresis Transporter Nephrons Nephron Kidney Cell biology medicine.anatomical_structure medicine Animals Phosphorylation Solute Carrier Family 12 Member 3 Cotransporter Claudin Research Article |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00014.2021 |
| Popis: | The renal nephron consists of a series of distinct cell types that function in concert to maintain fluid and electrolyte balance and blood pressure. The renin-angiotensin system (RAS) is central to Na(+) and volume balance. We aimed to determine how loss of angiotensin II signaling in the proximal tubule (PT), which reabsorbs the bulk of filtered Na(+) and volume, impacts solute transport throughout the nephron. We hypothesized that PT renin-angiotensin system disruption would not only depress PT Na(+) transporters but also impact downstream Na(+) transporters. Using a mouse model in which the angiotensin type 1a receptor (AT(1a)R) is deleted specifically within the PT (AT(1a)R PTKO), we profiled the abundance of Na(+) transporters, channels, and claudins along the nephron. Absence of PT AT(1a)R signaling was associated with lower abundance of PT transporters (Na(+)/H(+) exchanger isoform 3, electrogenic Na(+)-bicarbonate cotransporter 1, and claudin 2) as well as lower abundance of downstream transporters (total and phosphorylated Na(+)-K(+)-2Cl(−) cotransporter, medullary Na(+)-K(+)-ATPase, phosphorylated NaCl cotransporter, and claudin 7) versus controls. However, transport activities of Na(+)-K(+)-2Cl(−) cotransporter and NaCl cotransporter (assessed with diuretics) were similar between groups in order to maintain electrolyte balance. Together, these results demonstrate the primary impact of angiotensin II regulation on Na(+) reabsorption in the PT at baseline and the associated influence on downstream Na(+) transporters, highlighting the ability of the nephron to integrate Na(+) transport along the nephron to maintain homeostasis. NEW & NOTEWORTHY Our study defines a novel role for proximal tubule angiotensin receptors in regulating the abundance of Na(+) transporters throughout the nephron, thereby contributing to the integrated control of fluid balance in vivo. |
| Databáze: | OpenAIRE |
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