Bioactivity and metabolism of C-type natriuretic peptide in normal man.

Abstract

C-Type natriuretic peptide (CNP) is a recently identified member of the natriuretic peptide family with potent vasodepressor activity in experimental animals. Specific CNP receptors and gene transcripts have been identified in human vascular tissues, but the bioactivity and metabolism of CNP in humans are unknown. Accordingly, we have studied the renal, hormonal, and hemodynamic responses in nine normal men (seated, nonfasting) receiving a morning infusion (2 h) of synthetic human CNP-22 (5 pmol/kg.min) or placebo in single blind, random order. To determine the vasodepressor action, the effect of a second identical (afternoon) infusion on the pressor and hormone responses to angiotensin-II (2, 4, and 8 ng/kg.min each for 30 min) was also studied. In the morning infusion, plasma CNP increased from undetectable baseline levels to plateau levels (mean, 60 +/- 6 pmol/L) at 30-120 min. The mean MCR was 4.8 +/- 0.7 L/min, and the t 1/2 (plasma) was 2.6 min. Compared with the effects of placebo, there were significant increases in plasma cGMP (P = 0.001) and plasma atrial natriuretic peptide (ANP; P = 0.02) and a significant decrease in plasma aldosterone (P = 0.007). No significant hemodynamic action or natriuresis was observed. During coinfusion of angiotensin-II, the expected pressor and aldosterone responses were not significantly altered by CNP. In contrast to atrial and brain natriuretic peptide, short term infusion of CNP in humans, achieving supraphysiological levels in plasma, are not vasodepressor or natriuretic. Increases in plasma ANP and plasma cGMP and inhibition of aldosterone may be due in part to competitive displacement by CNP of ANP in common degradative pathways.

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

“…CNP is primarily known to stimulate long bone growth (Mericq et al, 2000). The half-life times of natriuretic peptides in the human circulation are ∼2-3 min for ANP and CNP (Hunt et al, 1994;Yandle et al, 1986) and 20 min for BNP (Mukoyama et al, 1990).…”

Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats

“…Bioactive CNP forms are rapidly degraded at source (and in plasma where the half-life of CNP 22 is w2 . 5 min in humans (Hunt et al 1994)…”

Release of C-type natriuretic peptide accounts for the biological activity of endothelium-derived hyperpolarizing factor

“…This 22-aa peptide is widely distributed in the cardiovascular system, being found in particularly high concentrations in vascular endothelial cells (11). CNP is a potent relaxant of vascular smooth muscle, particularly in the coronary circulation (14,15), and also inhibits smooth muscle cell proliferation (16) and aldosterone production (17,18). The cardiovascular actions of CNP are mediated via activation of the NPR subtypes, NPR-B (for which it is the preferential ligand) and NPR-C (19), the latter accounting for Ϸ95% of NPRs expressed in vivo (20).…”