Blockade of the hydroosmotic effect of vasopressin normalizes water excretion in cirrhotic rats.
Water retention in cirrhosis has classically been considered to be due to a low distal fluid delivery secondary to increased proximal sodium reabsorption. However, recent studies showing high plasma vasopressin levels in patients and rats with cirrhosis, ascites, and dilutional hyponatremia suggest that a nonosmotic vasopressin hypersecretion could be an alternative mechanism. To investigate the role of vasopressin in water retention in cirrhosis, the renal ability to excrete a water load (50 ml/kg body wt), as estimated by the minimum urinary osmolality and the percentage of the water load excreted during 3 h, was assessed in 10 control rats and in 20 cirrhotic rats with ascites and impaired water excretion and high urinary excretion of vasopressin. Twenty-four hours later, the same procedure was repeated in cirrhotic rats 20 min after the subcutaneous injection (30 micrograms/kg body wt) of d(CH2)5Tyr(Et) VAVP, an antagonist of the hydroosmotic effects of vasopressin (10 rats), or the vehicle (10 rats). Treatment with the vasopressin antagonist normalized water excretion in 9 of the 10 rats. No significant changes in renal water metabolism were observed in the group of rats given the vehicle. These results indicate that vasopressin hypersecretion is the predominant mechanism of the impairment in water excretion in rats with experimental cirrhosis and ascites.
Claria
J
J
Hormonal Laboratory and Liver Unit, Hospital Clínic i Provincial, Barcelona, Spain.
Jiménez
W
W
Arroyo
V
V
Guarner
F
F
López
C
C
La Villa
G
G
Asbert
M
M
Rivera
F
F
Rodés
J
J
D000818:Animals; D001127:Arginine Vasopressin / Q000627:therapeutic use / Q000031:analogs & derivatives; D004231:Diuresis / Q000187:drug effects; D007668:Kidney / Q000502:physiology; D008106:Liver Cirrhosis, Experimental / Q000150:complications*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy* / Q000209:etiology
D014667:Vasopressins; D001127:Arginine Vasopressin; C028884:1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-arginine vasopressin