Previous work (Levi et al. Kidney Inter. 23:489, 1983) identified an AVP-independent decrease in urinary concentrating ability of rats given a standard diet, ad lib water and dihydrotachysterol (DHT) (4.25 mg/kg of diet). Since increases in IMCD Purea and Pf are elicited by AVP, we used a similar experimental design to investigate the effects of DHT-induced hypercalcemia on IMCD components of the concentrating mechanism. As compared to matched controls (C), DHT rats (n=29) exhibited significant (p<0.05) increases in serum calcium (12.6±0.1 vs 9.6±0.1 mg/dl), sodium(137.4±1.0 vs 133.5±1.0 mM) and osmolality (288±1.6 vs 280.1±2.9 mOsm/L) accompanied by a reduced urine osmolality(771.5±56 vs 1067±81 mOsm/L). The basal Pf (252±33μM/sec n=6) of isolated perfused IMCD from DHT rats did not increase significantly after AVP (10-10 or 10-8 M). The IMCD of C rats(n=6) exhibited a significant 7 fold increase in Pf after AVP. In contrast, IMCD Purea (10-5 cm/sec n=5) from DHT vs C rats revealed significant increases in both basal (91±10 vs 48±8) and AVP (139±7 vs 101±7) values. Immunoblotting of DHT vs C IMCD showed a significant reduction in AQP-2 (87±4% n=4) protein but a 41±11% (n=5) increase in UT-2 content. Since our previous data (Sands, et al. J. Clin. Invest. In press. 1997) show that increases in IMCD intraluminal Ca2+ reduce AVP-elicited Pf, probably via an activated apical calcium/polyvalent cation receptor protein (CaR), we examined whether this CaR protein was altered in IMCD of DHT vs C rats. Immunoblotting with CaR antiserum reveals a marked shift of CaR bands to form a distinct high molecular weight complex in DHT not present in C rats. We conclude that AVP-elicited IMCD urinary concentrating components in DHT rats undergo a reduction in Pf and AQP-2 expression but an increase in Purea and UT-2 expression as compared to normocalcemic C rats. These changes in IMCD transepithelial transport are accompanied by a specific alteration in CaR protein. These data provide support for a role of these adaptive responses in preventing renal stone formation in sustained hypercalcemia.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Flores, F., Kato, A., Baum, M. et al. Hypercalcemia Selectively Decreases Rat Inner Medullary Collecting Duct(IMCD) Vasopressin (AVP)-Elicited Water Permeability (Pf) and Aquaporin-2 (AQP-2) Water Channel Protein Content While Increasing Its Urea Permeability (Purea) and the UT-2 Urea Channel Protein Content • 1650. Pediatr Res 41 (Suppl 4), 277 (1997). https://doi.org/10.1203/00006450-199704001-01669
Issue Date:
DOI: https://doi.org/10.1203/00006450-199704001-01669