Urotensin II Immunoreactivity in the Human Circulation: Evidence for Widespread Tissue Release

BACKGROUND: The sources of secretion and clearance of plasma urotensin II (UII) in the human circulation remain uncertain and may be relevant to understanding the role of UII in human physiology and cardiovascular disease. METHODS: In 94 subjects undergoing clinically indicated cardiac catheterization, we collected blood samples from arterial and multiple venous sites to measure transorgan gradients of plasma UII immunoreactivity. RESULTS: Net UII release occurred (in descending order of proportional transorgan gradient) across the heart, kidney, head and neck, liver, lower limb, and pulmonary circulations (P < 0.01). Although no specific clearance site was localized, the absence of an overall subdiaphragmatic aorto-caval peptide gradient indicated that there were lower body segment sites of UII clearance as well as secretion. The proportional increase in UII immunoreactivity was significantly correlated across all sites of net peptide release within an individual (P < or = 0.05). In univariate analyses, mixed venous UII concentrations were correlated with diagnosis of acute coronary syndrome and femoral artery oxygen tension and inversely with systolic blood pressure and body mass index. Diagnosis of acute coronary syndrome and body mass index were independent predictors of mixed venous UII immunoreactivity in multivariate analysis. No correlates of net cardiac UII release were identified. CONCLUSIONS: UII is secreted from the heart and multiple other tissues into the circulation. Related increments in UII immunoreactivity across multiple tissue sites suggest that peptide release occurs via a shared mechanism. Increased UII immunoreactivity is observed in subjects with acute coronary syndrome.