Increase in collecting duct basal:apical AQP2 protein expression ratio with increasing depth along the corticopapillary axis positively correlates with maximum urine concentrating capacity in the kangaroo rat and Sprague‐Dawley rat (1137.2)

Abstract

Our goal is to investigate the role of aquaporin 2 (AQP2) membrane expression in inner medullary (IM) collecting ducts (CD) relative to the urine concentrating mechanism by comparing basal‐to‐apical (B:A) AQP2 ratios of kangaroo rats (KR) with control and water‐restricted Sprague‐Dawley (SD). Previous studies have shown that vasopressin increases IMCD transepithelial water permeability, with apical AQP2 considered rate‐limiting, while in MCDK cells AQP2 is translocated to the basal membrane with hypertonicity and forskolin. The latter is seemingly inconsistent with the known role of AQP2. IM transverse sections at 1000‐µm intervals throughout the corticopapillary axis were labeled by immunohistochemistry for AQP2. The B:A AQP2 ratio at increasing 1000‐µm intervals from the IM border to papilla tip is ~2‐fold greater at each level in KR CD (.71, 1.23, 1.46, 1.18, 1.40, 1.51) relative to SD control (.46, .62, .65, .80, .88, 1.08) and SD water‐restricted (SDWR)(.41, .54, .54, .64, .54, .77). These results correlate with prior studies by others indicating peritubular hypertonicity elevates CD water permeability and B:A AQP2 ratios. Immunohistochemistry suggests a steady presence of basal AQP2 in KR and SDWR. Our data suggest a more significant role for basal AQP2 than presently realized. NIDDK DK083338, NSF 1OS095285, APS/NIDDK STEP‐UP, WAESO