Back to Search
Start Over
Impact of angiotensin II-mediated stimulation of sodium transporters in the nephron assessed by computational modeling
- Source :
- Am J Physiol Renal Physiol
- Publication Year :
- 2019
- Publisher :
- American Physiological Society, 2019.
-
Abstract
- Angiotensin II (ANG II) raises blood pressure partly by stimulating tubular Na+ reabsorption. The effects of ANG II on tubular Na+ transporters (i.e., channels, pumps, cotransporters, and exchangers) vary between short-term and long-term exposure. To better understand the physiological impact, we used a computational model of transport along the rat nephron to predict the effects of short- and long-term ANG II-induced transporter activation on Na+ and K+ reabsorption/secretion, and to compare measured and calculated excretion rates. Three days of ANG II infusion at 200 ng·kg−1·min−1 is nonpressor, yet stimulates transporter accumulation. The increase in abundance of Na+/H+ exchanger 3 (NHE3) or activated Na+-K+-2Cl− cotransporter-2 (NKCC2-P) predicted significant reductions in urinary Na+ excretion, yet there was no observed change in urine Na+. The lack of antinatriuresis, despite Na+ transporter accumulation, was supported by Li+ and creatinine clearance measurements, leading to the conclusion that 3-day nonpressor ANG II increases transporter abundance without proportional activation. Fourteen days of ANG II infusion at 400 ng·kg−1·min−1 raises blood pressure and increases Na+ transporter abundance along the distal nephron; proximal tubule and medullary loop transporters are decreased and urine Na+ and volume output are increased, evidence for pressure natriuresis. Simulations indicate that decreases in NHE3 and NKCC2-P contribute significantly to reducing Na+ reabsorption along the nephron and to pressure natriuresis. Our results also suggest that differential regulation of medullary (decrease) and cortical (increase) NKCC2-P is important to preserve K+ while minimizing Na+ retention during ANG II infusion. Lastly, our model indicates that accumulation of active Na+-Cl− cotransporter counteracts epithelial Na+ channel-induced urinary K+ loss.
- Subjects :
- Male
medicine.medical_specialty
Physiology
Sodium
Natriuresis
chemistry.chemical_element
Blood Pressure
Stimulation
Nephron
Lithium
Kidney Tubules, Proximal
Internal medicine
medicine
Animals
Computer Simulation
Epithelial Sodium Channels
Solute Carrier Family 12, Member 1
Kidney Medulla
Kidney
urogenital system
Sodium-Hydrogen Exchanger 3
Reabsorption
Chemistry
Angiotensin II
Membrane Transport Proteins
Nephrons
Rats
medicine.anatomical_structure
Endocrinology
Creatinine
Potassium
Cotransporter
Research Article
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 317
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....7ab3f3082ae95ae25c64dc255cd6381d
- Full Text :
- https://doi.org/10.1152/ajprenal.00335.2019