Regulation of acid-base balance in Dahl Salt-sensitive rats on normal- and high-salt diets

Acid-base homeostasis is essential for normal physiological function. Previous studies suggested that salt sensitivity in humans is associated with abnormal acid-base regulation. Here, we aim to use Dahl salt-sensitive (SS) rats to evaluate the response of kidneys to acid-loading under normal salt (0.4% NaCl, NS) and high salt (4% NaCl, HS) conditions. For the NS group, 10-week-old male and female rats were given 0.28 M NH 4 Cl with 1% sucrose in drinking water for 8 days. For the HS group, 8-week-old male and female rats were first fed with a HS diet for 3 weeks and then given 0.28 M NH 4 Cl with 1% sucrose in drinking water for 8 days. Tail vein blood and 24 hr urine were collected at days 0, 3, and 8 of the acid-loading. Results showed that male HS rats had significantly lower blood pH but similar blood HCO 3 - before acid-loading compared to NS rats. Acid-loading significantly decreased the blood pH of both male rats fed NS (7.39 ± 0.02 vs 7.27 ± 0.09; day 0 vs day 3) and HS (7.37 ± 0.01 vs 7.15 ± 0.06; day 0 vs day 3), with the blood pH of male HS rats remained significantly lower than the NS rats throughout the acid-loading period. Interesintly, although the acid loading significantly decreased the blood HCO 3 - of both male NS (27.3 ± 2.3 vs 17.9 ± 3.7; day 0 vs day 3) and HS (27.4 ± 0.5 vs 13.9 ± 2.2; day 0 vs day 3) rats, male NS rats completely recovered on day 8. No differences in blood pH or HCO 3 - were observed between female NS and HS rats before acid-loading. Similar to male rats, while acid-loading significantly lowered the blood pH and HCO 3 - of both female NS and HS rats on day 3, NS rats completely recovered the blood HCO 3 - on day 8. On the other hand, male HS rats exhibited significantly higher urine pH (5.7 ± 0.1 vs 5.6 ± 0.1; HS vs NS) but lower urinary NH 4 + (8.7 ± 3.5 vs 33.0 ± 11.4; HS vs NS) before acid-loading, with acid-loading significantly lowered urine pH and elevated urinary NH 4 + of male NS and HS rats on days 3 and 8. Additionally, urinary NH 4 + in male HS rats remained significantly lower than in rats fed NS diet throughout the acid-loading period. Female HS rats had similar urine pH but significantly lower urinary NH 4 + (10.7 ± 4.8 vs 34.6 ± 7.2; HS vs NS) compared to female NS rats before acid loading. Further more, acid-loading significantly increased the urinary NH 4 + in both female NS (34.6 ± 8.5 vs 80.0 ± 26.6; day 0 vs day 3) and HS (10.7 ± 4.8 vs 41.2 ± 4.5; day 0 vs day 3) rats on day 3. In summary, before acid-loading, male HS rats had significantly lower blood pH, higher urine pH, and lower urinary NH 4 + compared to NS rats, while female HS rats had similar blood and urine pH but significantly lower urinary NH 4 + compared to NS rats. During the acid-loading, both male and female HS rats showed impaired acid-base regulation compared to NS rats. Ongoing studies focus on evaluating the changes in key transporters in acid-base regulation in the kidney both before and after the acid-loading. National Institute of Health Grants R01 DK135644 (to AS) and Department of Veterans Affairs grant I01 BX004024 (to AS). This abstract was presented at the American Physiology Summit 2025 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.