Comparative bioactivity of atrial, brain and c-type natriuretic
peptides in conscious sheep.
Charles, Christopher J., Eric A. Espiner, A. Mark Richards, M. Gary
Nicholls, Timothy G. Yandle.
Department of Medicine, Christchurch Hospital, Christchurch, NEW
ZEALAND
APStracts 3:0019R, 1996.
While atrial natriuretic peptide (ANP) and brain natriuretic peptide
(BNP) appear to share functional homology, there is doubt concerning
a possible endocrine function for C-type natriuretic peptide (CNP)
and the relative potency of species specific forms of these hormones.
Accordingly, we have examined the biological effects, interactions
and pharmacokinetics of equimolar doses (0.5 followed by 2.5
pmol/kg/min each for 2h) of species specific forms of ANP, BNP-26 and
CNP-22 in vehicle controlled studies in normal conscious sheep.
Whereas pharmacokinetics (metabolic clearance rates of 5.7+1.17,
7.5+1.36 and 4.7+0.71 L/min and half-lives of 3.9+0.42, 2.5+0.21 and
2.0+0.18 min for ANP, BNP and CNP respectively) are similar, the
biological effects and actions on endogenous natriuretic peptide
levels differ. Plasma BNP was significantly increased by CNP infusion
(p<0.0001) as was CNP by BNP infusions (p=0.0009). Compared with
ANP and BNP, which were equipotent in stimulating plasma cyclic GMP
(p<0.0001 for both) and lowering arterial pressure (p<0.05
for both) and cardiac output, CNP infusions induced only a small
increment in cyclic GMP and had no significant hemodynamic actions.
In contrast, all three peptides suppressed plasma aldosterone levels
(p<0.05 for each) yet none induced significant natriuresis.
Actions of CNP to increase BNP (and ANP) may account for the observed
bioactivity of CNP. The findings show that potentially important
interactions occur among all three hormones which need to be
considered when interpreting the effects of individual peptides,
particularly CNP.
Received 30 January 1995; accepted in final form 29 December
1995.
APS Manuscript Number R76-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96