What is the clinical evidence from this study?

Study design: Other. Population: Salt-induced hypertension (n=48). Intervention: High-salt diet vs. 0.4% NaCl diet. Primary outcome: Mitochondrial respiration rates (JO2).

What question did this study set out to answer?

This research investigates how high salt diets affect mitochondrial function and blood pressure in normal versus salt-sensitive rats.

May 14, 2026

Differential Adaptation of Kidney Proximal Tubular Mitochondria to High Salt Diets in Normal Sprague Dawley and Dahl Salt-Sensitive Rats

Key Result

A high-salt diet increased mitochondrial respiration in normal rats, but in salt-sensitive rats, an initial increase at 7 days was followed by a significant decline at 14 and 21 days.

Key Points

This research investigates how high salt diets affect mitochondrial function and blood pressure in normal versus salt-sensitive rats.
Male Sprague-Dawley and Dahl salt-sensitive rats (n=6 per group) were fed low or high salt diets for 7, 14, and 21 days.
Mitochondrial respiration rates were measured using an Oroboros oxygraph with substrates for respiration complexes.
Mitochondrial oxygen consumption was assessed under different energization states.
Salt-sensitive rats showed increased mitochondrial oxygen consumption during high salt intake but decreased efficiency at longer durations compared to controls.
Normal Sprague-Dawley rats did not show significant changes in mitochondrial activity with high salt intake but trended towards increased oxygen consumption.
Efficiency in mitochondrial energy production declined in salt-sensitive rats, correlating with increased blood pressure.

Structured PICO

Does a high-salt diet alter mitochondrial bioenergetics in the proximal tubules of salt-sensitive rats compared to normal rats?

Population

Male Sprague-Dawley (SD) rats and Dahl salt-sensitive (SS) rats (n=6 per group), 9-10 weeks of age

Intervention

High-salt diet (4.0% NaCl) for 7, 14, and 21 days

Comparator

Low-salt diet (0.4% NaCl)

Outcome

Mitochondrial respiration rates (JO2) in permeabilized proximal tubulessurrogate

An inherent failure in kidney proximal tubule mitochondrial bioenergetics during chronic high-salt intake may underlie the development of salt-induced hypertension in salt-sensitive individuals.

Abstract

Background: Kidney proximal tubules (PTs) reabsorb nearly 65% of filtered Na + in the cortical region. With high-salt (HS) intake, added metabolic stress is placed upon PT mitochondria, increasing O 2 consumption and ATP production to meet the heightened energy demand. While mitochondrial bioenergetic alterations linked to HS diets and salt-sensitive (SS) hypertension are recognized, the temporal progression of these adaptive changes (short- versus long-term) in the PT and their consequences on blood pressure and salt sensitivity have not been characterized. The present study determined the progressive effects of HS intake on mitochondrial bioenergetics in the PT of normal Sprague-Dawley (SD) and Dahl SS rats to identify mechanisms underlying susceptibility to salt-induced hypertension. Methods: Male SD rats and Dahl SS rats (n=6 per group) were fed either a 0.4% NaCl diet (LS) or a 4.0% NaCl diet for 7, 14, and 21 days (HS7, HS14, and HS21, respectively). The average 24-hour mean arterial pressure of SS rats increased significantly with the HS diet, while SD rats showed no significant difference. At 9-10 weeks of age, PTs were isolated from the kidney cortex by collagenase digestion and sieving, then permeabilized through shear stress. Mitochondrial respiration rates (JO 2 ) were measured in the permeabilized PT using an Oroboros oxygraph by energizing with substrates for complex I (pyruvate+malate; PM) or complex II (succinate) to assess the state 2 (S2) JO 2 , followed by ADP stimulation (state 3; S3 JO 2 ), and uncoupling with FCCP (state 5; S5 JO 2 ). In a parallel protocol, JO 2 was studied in permeabilized PTs by providing sequential and incremental doses of ADP after substrate energization to induce stress. Results: Permeabilized PTs of SS rats showed an increase in S3 JO 2 in HS7, with significant decreases in S3 and S5 JO 2 in the HS14 and HS21 groups compared to the LS group when energized with PM and succinate. This was accompanied by significantly longer S3 JO 2 durations, indicating overall mitochondrial inefficiency in oxidative phosphorylation and coupling during the chronic phase of HS feeding in SS rats. In contrast, JO 2 was not significantly affected by HS intake in SD rats, although a trend toward increased JO 2 with progressive HS intake was observed. With sequential ADP doses, S3 JO 2 was significantly increased with HS in SD rats, while a significant decline was seen in SS rats at day 14 and day 21 of HS intake, compared to their respective LS controls. Conclusion: Increased metabolic work caused by a HS diet led to a rise in mitochondrial JO 2 in normal SD rats. In contrast, SS rats, although they increased JO 2 within 7 days to meet energy demands, failed to sustain this increase in the later stages of HS intake and subsequently declined. This decline in the efficiency in mitochondrial energy production is associated with the development of hypertension in the HS-fed SS rats. These results suggest that an inherent failure in mitochondrial bioenergetics could explain the salt-induced hypertension in SS individuals. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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