Acute Alcohol Withdrawal Increased Sodium Chloride Co-Transporter Expression in Rat Kidneys

Alcohol has been demonstrated to disrupt electrolyte balance and hemodynamics. However, there is a lack of findings displaying cohesive changes at the cellular level. Many cellular functions depend upon maintaining the homeostatic balance of ions and water, a primary responsibility of the kidneys. However, molecular mechanisms underlying electrolyte imbalances are unknown during alcohol intoxication and withdrawal. The aim of the present study was to determine the changes in the expression of renal sodium transporters along the nephron during acute withdrawal from chronic alcohol intoxication. To achieve this goal, we treated 10-week-old male and female Sprague-Dawley rats with 30% alcohol (from 95% stock solution, 5gm/kg body weight) three times a day for 4 days, followed by a withdrawal period of 24 or 48 hours. Following anesthesia with isoflurane, the kidneys were removed and decapsulated, and crude membranes were prepared. Expression of sodium-potassium ATPase a1 subunit (ATP1a1, NKA), sodium chloride cotransporter (Slc12a3, NCC), water channel Aquaporin-2 (Aqp2), and sodium-calcium exchanger (Slc8A1, NCX1) were determined by western blotting. The results demonstrated that NKA expression and activity were significantly higher in control females compared to males. An increase in NKA expression and activity was observed in males but not in females 24 hrs after alcohol withdrawal. Interestingly, both expression and activity of NKA returned to control levels 48 hrs after alcohol withdrawal. The expression levels of NCC were higher in both males and females but more prominently in females than in males 24 and 48 hrs following alcohol withdrawal. NCX1 expression was significantly higher in females than in males. NCX1 expression increased following 24 hrs alcohol withdrawal but returned to control levels 48 hrs after alcohol withdrawal. In contrast to NKA and NCC, the expression of Aqp2 was similar to control levels in both males and females 24 hrs after alcohol withdrawal but decreased 48 hrs following alcohol withdrawal. Our findings reveal previously unknown effects of acute alcohol withdrawal on kidney function, specifically increasing the expression of NCC and NCX1 while decreasing Aqp2 expression in the kidneys. Further studies are needed to determine the pathophysiological significance of these changes. Supported by NIH grant R01 AA027660 (PN) and 5R21AG047474 (SJK), and AHA grant GIA, 16GRNT31030019 (SJK) 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.