Brain natriuretic peptide: pathophysiologic and potential
therapeutic roles in acute congestive heart failure.
Grantham, J. Aaron, Daniel D. Borgeson, and John C. Burnett, Jr.
The Cardiorenal Research Laboratory, Division of Cardiovascular
Diseases, Mayo Clinic, Rochester, MN
APStracts 3:0418R, 1996.
Controversy persists regarding the acute responsiveness of atrial
(ANP) and brain (BNP) natriuretic peptides in pathophysiological
conditions such as acute heart failure (AHF). The current study was
designed to test the hypothesis that AHF is characterized by
selective activation of ANP, but not BNP. We also hypothesized that
BNP replacement in AHF would reduce cardiac filling pressures,
increase sodium excretion and inhibit circulating renin. Two groups
of anesthetized dogs underwent rapid left ventricular pacing to
induce AHF. Group 1 (n=7) served as control and group 2 (n=7)
received canine BNP (10 ng/kg/min). Cardiorenal parameters,
circulating natriuretic peptides, 3',5'-cyclic guanosine
monophosphate (cGMP), and plasma renin activity (PRA) were determined
at baseline and during AHF in both groups. AHF was characterized by
reductions in cardiac output (CO) (2.3+/-0.2 vs 3.7+/-0.3 L/min,
p<0.05), pulmonary capillary wedge pressure (PCWP) (11.7+/-0.8
vs 5.1+/-0.3 mmHg, p<0.05), and selective activation of ANP
(250+/-51 vs 39+/-13 pg/ml, p<0.05) with no increase in
circulating BNP (49+/-15 vs 50+/-16 pg/ml, p=ns). When compared to
control, exogenous supplemental BNP in AHF resulted in marked
increases in circulating cGMP (65+/-6 vs 18+/-5 pg/ml, p<0.05)
with reductions in PCWP (9.1+/-0.9 vs 12.9+/-1.1 mmHg, p<0.05)
and increased urinary sodium excretion (UNaV) (120+/-36.8 vs 24+/-6.3
ueq/min, p<0.05) via reductions in distal tubular sodium
reabsorption (94.3+/-1.8 vs 98.0+/-0.4 %, p<0.05 ). Exogenous
BNP prevented the increase in PRA that occurred in the control group.
We conclude that AHF is characterized by a failure to increase
circulating BNP underscoring differential physiological and
pathophysiological roles for ANP and BNP in states of immediate
cardiac overload. These studies also support a potential role for BNP
in the therapeutics of AHF.
Received 8 July 1996; accepted in final form 4 November 1996.
APS Manuscript Number R388-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996