We determined whether aquaporin of collecting duct (AQP-CD) is involved in pathogenesis of water retention in rats with experimental models of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and liver cirrhosis. SIADH rats were made by administering 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously and providing them with a liquid diet. Serum Na levels decreased to < 120 meq/l on day 2, and hyponatremia persisted throughout the rest of observation period. Six hours after the DDAVP infusion, the expression of AQP-CD mRNA significantly increased by 198%, followed by > 144% increases in its expression during the 14-day observation period. On day 7, the increased expression of AQP-CD mRNA was abolished after the administration of an antidiuretic, nonpeptide arginine vasopressin (AVP) antagonist, OPC-31260, which was closely related to a marked diuresis and a prompt normalization of serum Na levels in SIADH rats. Rats were made cirrhotic by injecting a mixture of carbon tetrachloride and olive oil subcutaneously for 3 mo. The expression of AQP-CD mRNA was increased by 164% in the decompensated cirrhotic rats. The blockade of AVP action by OPC-31260 significantly diminished its expression. These results indicate that water channel AQP-CD plays an important role in water retention in pathological states of SIADH and liver cirrhosis.

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Dehydration increased the expression of aquaporin of collecting duct (AQP-2) and translocated AQP-2 to the apical plasma membranes from cytoplasmic vesicles of collecting duct cells. We determined whether the abrupt decrease in circulating arginine vasopressin (AVP) by giving excess water affects the expression of AQP-2 mRNA and subcellular localization of AQP-2 in collecting duct cells of the dehydrated rats. The 72-h water deprivation increased plasma AVP levels to 3.1 pg/ml and the expression of AQP-2 mRNA by 336% in rats, which were concomitantly abolished by the 40 ml/kg oral water load. A 50% inhibition ofAQP-2 mRNA expression was obtained with 20 min after the forced water load. In immunohistochemistry and electron microscopy, the AQP-2 was manifestly present around the apical edge of collecting duct cells in the 72-h dehydrated rats. The AQP-2 was diffusely translocated into the cytoplasm 1 h after the forced water administration. These results indicate that AVP plays the on-off regulation of AQP-2 mRNA expression and that a majority of AQP-2 is regulated by the shuttle recycling in the collecting duct cells.

HCO3 concentration was increased from 25 to 40 mM without changing peritubular Pco2, a 45% reduction in HCO-reabsorption was observed. This inhibitory effect of increasing peritubular HCO3 concentration was reversed when peritubular pH was normalized by increasing Pco2. Passive permeability for HCO-was also measured and found to be 1.09±0.17 X 10-7 cm2 s-'. Using this value, the passive flux of HCO-could be calculated. Only a small portion (<23%) of the observed changes in net HCO-reabsorption can be explained by the passive HCO-flux. We conclude that luminal and peritubular HCO3 concentrations alter HCO-reabsorption by changing the active H+ secretion rate. Analysis of these data suggest that both luminal and peritubular pH are major determinants of HCO-reabsorption.

The effects of acidosis and mineralocorticoids on cellular H+/ HCO3 transport mechanisms were examined in intercalated cells of the outer stripe of outer medullary collecting duct (OMCDo) from rabbit. Intracellular pH (pHi) of intercalated cells was monitored by fluorescence ratio imaging using 2',7-