Nonosmotic release of vasopressin and renal aquaporins in impaired urinary dilution in hypothyroidism.
The purpose of this study was to examine protein expression of renal aquaporins (AQP) and ion transporters in hypothyroid (HT) rats in response to an oral water load compared with controls (CTL) and HT rats replaced with l-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration for 10 wk. Body weight, water intake, urine output, solute and urea excretion, and serum and urine osmolality were comparable among the three groups at the conclusion of the 10-wk treatment period. One hour after oral gavage of water (50 ml/kg body wt), HT rats demonstrated significantly less water excretion, higher minimal urinary osmolality, and decreased serum osmolality compared with CTL and HT+T rats. Despite the hyposmolality, plasma vasopressin concentration was elevated in HT rats. These findings in HT rats were associated with an increase in protein abundance of renal cortex AQP1 and inner medulla AQP2. AQP3, AQP4, and the Na-K-2Cl cotransporter were also increased. Moreover, 1 h following the oral water load, HT rats demonstrated a significant increase in the membrane-to-vesicle fraction of AQP2 by Western blot analysis. The defect in urinary dilution in HT rats was reversed by the V(2) vasopressin antagonist OPC-31260. In conclusion, impaired urinary dilution in HT rats is primarily compatible with the nonosmotic release of vasopressin and increased protein expression of renal AQP2. The impairment of maximal solute-free water excretion in HT rats, however, appears also to involve diminished distal fluid delivery.
Chen
Yung-Chang
YC
Univ. of Colorado School of Medicine, 4200 E. Ninth Ave., Box C293, Denver, CO 80262, USA.
Cadnapaphornchai
Melissa A
MA
Yang
Jianhui
J
Summer
Sandra N
SN
Falk
Sandor
S
Li
Chunling
C
Wang
Weidong
W
Schrier
Robert W
RW
D000640:Amitrole; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D051398:Aquaporin 1; D051399:Aquaporin 2; D051401:Aquaporin 4; D020346:Aquaporins / Q000378:metabolism*; D001693:Biological Transport, Active; D015153:Blotting, Western; D004452:Echocardiography; D006439:Hemodynamics / Q000502:physiology; D007037:Hypothyroidism / Q000139:chemically induced / Q000652:urine*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism*
D065092:Antidiuretic Hormone Receptor Antagonists; C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496032:Aqp4 protein, rat; D051399:Aquaporin 2; D051401:Aquaporin 4; D020346:Aquaporins; D017483:Receptors, Vasopressin; D014667:Vasopressins; D051398:Aquaporin 1; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D000640:Amitrole