Skeletal contributions to plasma CNP forms: Evidence from regional sampling in growing lambs

Unlike the cardiac circulating hormones, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) appears to be largely tissue-based and circulates at concentrations considered insufficient to affect organ function. Consistent with CNP's crucial role in regulating skeletal growth, serial studies in juveniles show that both plasma CNP and aminoterminal proCNP (NTproCNP) are highly correlated with growth velocity raising the possibility that skeletal tissues contribute to circulating concentrations of CNP forms during the growing period. Hypothesizing that venous blood draining from bone dense regions is relatively enriched in CNP, we have performed trans-organ regional blood sampling for measurement of CNP forms in 4-week-old lambs and compared the findings to simultaneous levels of ANP and BNP. Because bone growth and CNP synthesis are inhibited by glucocorticoids, identical studies were also undertaken in lambs pretreated with dexamethasone. Highly significant positive arterio-venous gradients of CNP were found across the head, heart, leg and foot. Dexamethasone significantly reduced the CNP arterio-venous gradient across the head and leg but not heart, liver or kidney. In contrast, there was no evidence of tissue secretion of ANP or BNP except across the heart, and no effect on these gradients from dexamethasone. These findings of CNP enrichment in samples from bone dense regions in growing lambs, and their selective reduction by dexamethasone, provide in vivo evidence linking plasma and skeletal tissue concentrations of CNP and further support the use of plasma CNP forms as markers of bone growth.