Regional release and clearance of C-type natriuretic peptides in the human circulation and relation to cardiac function.
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.
Palmer
Suetonia C
SC
Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand. suetoniapalmer@clear.net.nz
Prickett
Timothy C R
TC
Espiner
Eric A
EA
Yandle
Timothy G
TG
Richards
A Mark
AM
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000503:physiopathology*; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D020098:Natriuretic Peptide, C-Type / Q000097:blood* / Q000737:chemistry; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood / Q000737:chemistry; D011863:Radioimmunoassay
D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type