Arginine-vasopressin (AVP) activates water and electrolyte absorption in the collecting duct as well as electrolyte absorption in the thick ascending limb (TAL). In all renal tubules, which respond to AVP the hormone causes increases of cAMP and intracellular Ca²⁺. The V2 receptor is critical for most renal tubular actions of AVP. However, other AVP receptors (V1) are known to be expressed in TAL of certain mammalian species.

Objective: 

Investigate the effect of the highly specific V2 receptor antagonist satavaptan on AVP-stimulated NaCl transport in mouse medullary thick ascending limb (mTAL).

Methods: 

We used isolated, perfused mouse mTALs to electrically measure Na⁺ absorption. By electrodes we determined the transepithelial voltage (V_te) and the transepithelial resistance (R_te) and via these the transepithelial Na⁺ absorption (equivalent short circuit current, I_sc).

Results: 

Non-stimulated mTALs showed a lumen-positive transepithelial voltage (V_te) of +6.26±1.02 mV and a transepithelial resistance (R_te) of 3.05±0.45 W cm² resulting in an equivalent short circuit current (I_sc) of 2196±356 mA/cm² (n=5). Within 5–10 minutes basolateral AVP (10 nM) triggered a pronounced and ongoing activation of transport as seen by an increase of V_te to +11±0.71 mV and I_sc to 3460±475 mA/cm². R_te remained unaltered. In paired experiments satavaptan (1 mM) completely abolished the AVP-induced increase in V_te and I_sc (n=5). Satavaptan did not influence baseline mTAL transport.Conclusion: These are the first functional data in isolated perfused mTAL to quantify the effect of specific V2 antagonists on NaCl transport. They indicate that V2 receptor blockage is sufficient to suppress the entire AVP-activated NaCl absorption in mouse mTAL. Other vasopressin receptors appear not to be involved. Thus, the critical role of the V2 receptor for AVP-mediated transport activation is confirmed.