Objective: The aim of this study was to examine the regional myocardial var
iation in atrial natriuretic peptide (ANP) and brain natriuretic peptide (B
NP) synthesis during development of congestive heart failure (CHF). Methods
: Heart failure was induced by left atrial rapid pacing for 3 weeks in pigs
. The gene expression of ANP and BNP was measured by northern blot analysis
and the peptide concentration in myocardial tissue and plasma by radioimmu
noassay (RIA). Results: At the end of the pacing period pulmonary capillary
wedge pressure (PCWP) and right atrial pressure (RAP) increased, and cardi
ac output (CO) decreased compared to sham-operated controls (PCWP: 17.6+/-1
.9 vs. 3.1+/-0.9 mmHg) (RAP: 10.4+/-1.7 vs. 2.2+/-0.6 mmHg) (CO: 3.5+/-0.4
vs. 5.3+/-0.3 1/min), indicating a state of moderate to severe CHF. The gen
e expression and tissue concentration of BNP was low in sham pigs, but was
strongly increased in all cardiac regions, and especially in the left ventr
icle, during CHF. In contrast, ANP was mainly produced in the atria both in
normal and heart failure conditions. The relative increases in mRNA levels
, tissue concentrations and circulating peptide concentrations were more pr
ofound for BNP than for ANP. Conclusions: In response to CHF induction, ANP
and BNP respond differently across the cardiac regions. Strong expression
of the BNP gene was only found in the heart failure state, while ANP was cl
early expressed also in the normal state. These findings support the concep
t of BNP being superior to ANP as a biochemical marker of CHF.