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 '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.
Ishikawa
S
S
Department of Medicine, Jichi Medical School Omiya Medical Center, Saitama, Japan. saneiskw@jichi.ac.jp
Saito
T
T
Kasono
K
K
D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism*; D007010:Hyponatremia / Q000378:metabolism*; D007177:Inappropriate ADH Syndrome / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D051381:Rats; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology*
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D014867:Water