Upregulation of aquaporin-2 water channel expression in chronic heart failure rat.
Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.
Xu
D L
DL
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Martin
P Y
PY
Ohara
M
M
St John
J
J
Pattison
T
T
Meng
X
X
Morris
K
K
Kim
J K
JK
Schrier
R W
RW
D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins; D001552:Benzazepines / Q000494:pharmacology; D002908:Chronic Disease; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000378:metabolism*; D007150:Immunohistochemistry; D007473:Ion Channels / Q000032:analysis / Q000235:genetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood; D015854:Up-Regulation; D014882:Water-Electrolyte Balance
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D001552:Benzazepines; D007473:Ion Channels; C076251:mozavaptan; D012964:Sodium