Interactions of atrial and brain natriuretic peptides at
pathophysiological levels in normal men.
Hunt, P. J., E. A. Espiner, A. M. Richards, T. G. Yandle, C. Frampton,
M. G. Nicholls.
Department of Endocrinology, Christchurch Hospital, Private Bag,
Christchurch, New Zealand
APStracts 2:0187R, 1995.
Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP)
are both circulating plasma hormones that are secreted by the heart
and have similar physiological effects. We have shown previously that
abrupt increases in plasma BNP in normal humans impair the clearance
of ANP from plasma and result in additive physiological effects.
Since large increases in plasma ANP are reported to have no effect on
plasma BNP levels in patients with heart failure, we have studied
ANP/BNP interactions in 8 normal males receiving background infusions
of BNP (2pmol/kg/min for 5h). Each subject also received a co
-infusion of ANP ("active" day, 2 pmol/kg/min for 2h) or vehicle
("placebo" day) using a balanced random order, single blind design.
Metabolic clearance rate of ANP (mean 4.1+/-0.6L/min) and
disappearance rate from the plasma (t 3.4+/-0.3min) were similar to
values measured previously in the absence of exogenous BNP. In
contrast, steady state plasma BNP levels were reversibly increased
(mean BNP increment 10pmol/L) during the administration of ANP
(p=0.038). Associated with these changes were significant (additive )
physiological effects. Thus the addition of ANP increased plasma and
urine guanosine 3'-5' cyclic monophosphate (p<0.001 for both)
and lowered systolic blood pressure (p=0.049). When ANP was co
-infused, significant differences were also observed in urine volume
(p=0.001) and sodium excretion (p=0.043) between the infusion period
(when urine volume and sodium excretion were enhanced) and post
infusion period (when values decreased). Taken together, our findings
of similar interactions between ANP/BNP and BNP/ANP infusions
occurring at pathophysiological concentrations of these two peptides,
suggest that the interactions result from dissociation of prebound
hormone, presumably from biological or clearance receptors.
Received 7 February 1995; accepted in final form 27 June 1995.
APS Manuscript Number R98-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.