Pathological role of aquaporin-2 in impaired water excretion and hyponatremia

In the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), inappropriately elevated secretion of vasopressin can result in a reduction of antidiuretic efficacy: a phenomenon known as I vasopressin escape'. We compared experimental SIADH with 1-deamino-8-D-arginine vasopressin (dDAVP)-excess rats, where both groups received continuous subcutaneous administration of dDAVP by osmotic minipump but the SIADH rats also received a liquid diet that induced hyponatraemia. The SIADH rats, but not the dDAVP excess rats, showed a marked attenuation of urinary concentrating ability. Vasopressin V-2 receptor binding capacity and mRNA expression were similar between the two groups, but the SIADH rats showed a diminished up-regulation of aquaporin-2 (AQP-2) mRNA and protein expression. These findings indicate the presence of tonicity-response regions in the AQP-2 promoter gene, and that either hypervolemia or hypotonicity may attenuate the postreceptor signalling of vasopressin in renal collecting duct cells in SIADH rats.