Acute alcohol withdrawal increases sodium transporter expression in rat kidneys

Alcohol consumption is associated with elevated blood pressure and disturbances in electrolytes and water balance, with the kidneys playing key roles in regulating these functions. However, the renal mechanisms involved during both alcohol consumption and subsequent withdrawal remain insufficiently understood. The present study aimed to investigate changes in the expression of key renal proteins, specifically renal sodium chloride cotransporter (NCC), Na-K-ATPase α1-subunit (NKA), sodium-calcium exchanger (NCX1), and Aquaporin-2 (Aqp2) during acute alcohol withdrawal. To achieve this goal, adult male and female Sprague-Dawley rats were administered alcohol (30% vol/vol) three times a day for 4 days, followed by an active withdrawal period of 24 or 48 h. Control rats received a vehicle without alcohol. The expressions of NCC, NKA, NCX1, and Aqp2 were determined by western blotting in renal cortical crude membranes at 24 and 48 h into withdrawal. The results indicated that alcohol withdrawal increased NCC expression in both sexes at 24 and 48 h post-withdrawal. NKA expression was higher in control females compared to males, and at 24 h into alcohol withdrawal, NKA expression increased in males but not in females, returning to control levels by 48 h. A transient increase in NCX1 expression was observed in females but not in males at 24 h into alcohol withdrawal. Furthermore, Aqp2 expression consistently decreased in both sexes following alcohol withdrawal. These findings suggest that alcohol withdrawal increases the expression of NCC, NKA, and NCX1 in the kidneys, while concurrently decreasing Aqp2 expression, potentially contributing to kidney dysfunction associated with alcohol use.