Increased urinary excretion of uroguanylin in patients with congestive heart failure

Citation
Sl. Carrithers et al., Increased urinary excretion of uroguanylin in patients with congestive heart failure, AM J P-HEAR, 278(2), 2000, pp. H538-H547
Citations number
47
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
03636135 → ACNP
Volume
278
Issue
2
Year of publication
2000
Pages
H538 - H547
Database
ISI
SICI code
0363-6135(200002)278:2<H538:IUEOUI>2.0.ZU;2-9
Abstract
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.