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(Hypertension. 2009;54:612.)
© 2009 American Heart Association, Inc.

Original Articles

Regional Release and Clearance of C-Type Natriuretic Peptides in the Human Circulation and Relation to Cardiac Function

Suetonia C. Palmer; Timothy C.R. Prickett; Eric A. Espiner; Timothy G. Yandle; A. Mark Richards

From the Christchurch Cardioendocrine Research Group (T.C.R.P., E.A.E., T.G.Y., S.C.P., A.M.R.), Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.

Correspondence to Suetonia C. Palmer, Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch, New Zealand. E-mail suetoniapalmer{at}clear.net.nz

Production and clearance of plasma C-type natriuretic peptide (CNP) and amino terminal (NT)-proCNP immunoreactivity in the human circulation remain poorly characterized. Accordingly, we have measured arterial and venous concentrations of CNP and NT-proCNP across multiple tissue beds during cardiac catheterization in 120 subjects (age: 64.2±9.0 years; 73% men) investigated for cardiovascular disorders. The heart, head and neck, and musculoskeletal tissues made the clearest contributions to both plasma CNP and NT-proCNP (P<0.05). Net release of NT-proCNP was also observed from hepatic tissue (P<0.001). Negative arteriovenous gradients for CNP were observed across renal, hepatic, and pulmonary tissue (P<0.05), indicating net clearance, whereas no tissue-specific site of NT-proCNP clearance was identified. Age, mean pulmonary artery pressure, left ventricular end diastolic pressure, Brandt score of myocardial jeopardy, and troponin I were independent predictors of circulating CNP levels in multivariable analysis. Sex and kidney function were independently predictive of arterial NT-proCNP. The proportional step-up of CNP (+60%) across the heart was less than for brain natriuretic peptide (+123%) but greater than for NT–pro-brain natriuretic peptide (NT-proBNP) (+36%) and NT-proCNP (+42%; P<0.001 for all). We conclude that cardiac and head and neck tissue are important sources of CNP. Circulating CNP but not NT-proCNP concentrations are related to cardiac hemodynamic load and ischemic burden. Although cardiac release is most evident, multiple additional tissues release NT-proCNP immunoreactivity without evidence for an organ-specific site for NT-proCNP degradation. Taken together, differences in magnitude and direction of transorgan gradients for CNP compared with NT-proCNP suggest net generalized cosecretion with differing mechanisms of clearance.

Key Words: natriuretic peptides • circulation • plasma • glomerular filtration rate • human