Hydraulic water permeability and transepithelial voltage in the isolated perfused rabbit cortical collecting tubule following acute unilateral ureteral obstruction

Abstract

Ureteral obstrucion affects the kidney's ability to conserve water and sodium. Using the isolated perfused tubule technique, we studied cortical collecting tubules (CCT) taken from rabbits subjected to a sham operation or to 4 h of unilateral ureteral obstruction (UUO). Tubules were perfused in the presence of an osmotic gradient directed to promote water movement from lumen to bath, and volume flux (J(v)), hydraulic water permeability (L(p)), and transepithelial voltage (V(l)) were determined. In tubules from sham-operated and UUO animals, basal (before exposure to vasopressin) J(v) and L(p) were not different from zero. After addition of 200 μU.ml-1 of arginine vasopressin (aVP) to the bath, J(v) and L(p) increased to 1.64 ± 0.23 nl.mm-1.min-1 and 127.9 ± 19.8 cm.s-1.atm-1.107, respectively, in tubules from sham-operated animals, but to only 0.27 ± 0.09 nl.mm-1.min-1 and 18.8 ± 6.2 cm.s-1.atm-1.107 in tubules from UUO animals. Pretreatment with desoxycorticosterone acetate (DOCA) or indomethacin in vivo did not prevent the blunted vasopressin response seen in tubules taken from UUO animals. The J(v) and L(p) responses to the cyclic AMP (cAMP) analogue, 8-Br-cAMP, were also diminished in tubules taken from UUO animals compared with shams. V(l), measured during the basal period, was diminished in tubules from UUO kidneys (-5.0 ± 2.1 mV) compared with shams (-21.9 ± 4.1 mV), and pretreatment with DOCA did not prevent the effects of UUO on V(l). In contrast, tubules taken from animals that received indomethacin prior to UUO developed voltages not different from voltages in tubules taken from sham-operated animals (-17.3 ± 1.7 mV). We conclude that, although CCT from UUO animals can maintain osmotic gradients, their ability to respond to vasopressin by increasing L(p) is impaired by an intrinsic defect located at a step beyond the generation of cAMP, and that prostaglandin inhibition or DOCA pretreatment do not reverse the decreased responsiveness of L(p) to aVP. UUO also diminished V(l), and this abnormality was prevented by previous treatment with indomethacin, suggesting that prostaglandins may mediate the effect of UUO on V(l).