Effects of uroguanylin on natriuresis in experimental nephrotic rats.
OBJECTIVE
Uroguanylin, isolated from human and opossum urine, is a candidate intestinal natriuretic hormone that controls the sodium and water balance between the intestine and the kidneys. Levels of immunoreactive (ir)-uroguanylin in the plasma and urine are increased in rats and humans with nephrotic syndrome, which is physiologically characterized by sodium retention with massive proteinuria. The present study evaluates the effect of natriuresis induced by uroguanylin on nephrotic rats.


METHODS
Normal rats and rats rendered nephrotic by injections of puromycin aminonucleoside (PAN) were treated with uroguanylin (0.5 nmol/h, delivered by an osmotic pump) or with vehicle during the sodium retention phase. All rats consumed the same quantity of sodium.


RESULTS
Uroguanylin did not increase urinary excretion of sodium and water in normal rats, but significantly increased urinary sodium excretion during the sodium retention phase in nephrotic rats (untreated vs uroguanylin-treated nephrotic rats in mmol/mmol creatinine; 2.92 +/- 0.65 vs 8.93 +/- 2.53 on day 6, P < 0.05; 3.55 +/- 0.47 vs 10.37 +/- 1.73 on day 7, P < 0.01; 14.88 +/- 2.32 vs 24.47 +/- 2.86 on day 8, P < 0.05). Plasma levels of ir-uroguanylin in uroguanylin-treated nephrotic rats on day 6 were significantly increased compared with those in uroguanylin-treated control and untreated nephrotic rats.


CONCLUSIONS
Uroguanylin increased urinary sodium excretion in rats with PAN-induced nephrosis, and might be useful for treating sodium retention in patients with nephrotic syndrome.
Baba
Akiko
A
Department of Internal Medicine, University of Miyazaki, Japan. akikob@fc.miyazaki-u.ac.jp
Fujimoto
Shouichi
S
Kikuchi
Masao
M
Kita
Toshihiro
T
Kitamura
Kazuo
K
D000818:Animals; D006162:Guanylate Cyclase / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D045265:Natriuretic Peptides / Q000494:pharmacology*; D009404:Nephrotic Syndrome / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley
D045265:Natriuretic Peptides; C084362:uroguanylin; D006162:Guanylate Cyclase