AHEART February 47/2

Carrithers, Stephen L., Sammy L. Eber, Leonard R. Forte, and Richard N. Greenberg. Increased urinary excretion of uroguanylin in patients with congestive heart failure. Am. J. Physiol. Heart Circ. Physiol. 278: H538–H547, 2000.—Uroguanylin is a small-molecular-weight peptide that activates membrane-bound receptor-guanylate cyclases in the intestine, kidney, and other epithelia. Uroguanylin has been shown to participate in the regulation of salt and water homeostasis in mammals via cGMP-mediated processes, bearing a distinct similarity to the action of the atriopeptins, which play a defined role in natriuresis and act as prognostic indicators of severe congestive heart failure (CHF). The objectives of this study were to measure the urinary levels of uroguanylin and the circulating plasma levels of atrial natriuretic peptide (ANP) in healthy individuals (n 5 53) and patients with CHF (n 5 16). Urinary excretion of uroguanylin was assessed by a cGMP accumulation bioassay employing human T84 intestinal cells. In individuals without CHF, the concentration of uroguanylin bioactivity was 1.31 6 0.27 nmol cGMP/ml urine and 1.73 6 0.25 μmol cGMP/24-h urine collection. The urinary bioactivity of uroguanylin in males (1.74 6 0.55 nmol cGMP/ml urine; n 5 27) tended to be higher than the excretion levels in females (0.94 6 0.16 nmol cGMP/ml urine; n 5 26) over a 24-h period but did not achieve statistical significance. Both male and female groups showed 24-h temporal diurnal variations 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 6 1.6 pg/ml plasma and did not significantly vary with respect to male/female population or diurnal variation. In patients with CHF, the concentration of plasma ANP and urinary uroguanylin bioactivity increased substantially (7.5-fold and 70-fold, respectively, both P # 0.001) compared with healthy 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 prouroguanylin protein. The increased urinary uroguanylin excretion observed during CHF may be an adaptive response to this cardiovascular pathophysiology.