Uroguanylin is a small-molecular-weight peptide that activates membrane-bou
nd receptor-guanylate cyclases in the intestine, kidney, and other epitheli
a. Uroguanylin has been shown to participate in the regulation of salt and
water homeostasis in mammals via cGMP-mediated processes, bearing a distinc
t similarity to the action of the atriopeptins, which play a defined role i
n natriuresis and act as prognostic indicators of severe congestive heart f
ailure (CHF). The objectives of this study were to measure the urinary leve
ls of uroguanylin and the circulating plasma levels of atrial natriuretic p
eptide (ANP) in healthy individuals (n = 53) and patients with CHF (n = 16)
. Urinary excretion of uroguanylin was assessed by a cGMP accumulation bioa
ssay employing human T84 intestinal cells. In individuals without CHF, the
concentration of uroguanylin bioactivity was 1.31 +/- 0.27 nmol cGMP/ml uri
ne and 1.73 +/- 0.25 mu mol cGMP/24-h urine collection. The urinary bioacti
vity of uroguanylin in males (1.74 +/- 0.55 nmol cGMP/ml urine; n = 27) ten
ded to be higher than the excretion levels in females (0.94 +/- 0.16 nmol c
GMP/ml urine; n = 26) over a 24-h period but did not achieve statistical si
gnificance. Both male and female groups showed 24-h temporal diurnal variat
ions with the highest uroguanylin levels observed between the hours of 8:00
AM and 2:00 PM. The circulating level of ANP was 12.1 +/- 1.6 pg/ml plasma
and did not significantly vary with respect to male/female population or d
iurnal variation. In patients with CHF, the concentration of plasma ANP and
urinary uroguanylin bioactivity increased substantially (7.5-fold and 70-f
old, respectively, both P less than or equal to 0.001) compared with health
y levels. Uroguanylin was purified from the urine of CHF patients and shown
to be the bioactive, COOH-terminal, 16 amino acid portion of the human pro
uroguanylin protein. The increased urinary uroguanylin excretion observed d
uring CHF may be an adaptive response to this cardiovascular pathophysiolog
y.