Comparative Bioactivity of Atrial and Brain Natriuretic Peptides in An Ovine Model of Heart Failure

Abstract

1. Whereas many studies have detailed the effects of exogenous atrial natriuretic peptide (ANP) infusions in heart failure, and a limited number have examined the effects of brain natriuretic peptide (BNP), none have directly compared the bioactivity of similar doses of ANP and BNP under standard conditions of impaired cardiac function. We compared the hormonal, haemodynamic and renal effects of 3 h infusions of ANP, BNP and a vehicle control in eight sheep with pacing-induced heart failure (225 beats/min for 8-12 days). 2. Infusion of ANP and BNP increased plasma ANP (P < 0.001) (276 +/- 27 versus control 142 +/- 26 pmol/l) and BNP (P < 0.001) (257 +/- 34 versus control 45 +/- 5 pmol/l) respectively, in association with increased cyclic 3',5'-guanosine monophosphate [control, 40 +/- 6; ANP, 53 +/- 6 (P < 0.05); BNP, 57 +/- 7 nmol/l (P < 0.001)]. Metabolic clearance rate and half-life were similar for both peptides. Infusion of ANP and BNP similarly reduced mean arterial pressure [control, 73.0 +/- 1.6; ANP, 67.6 +/- 1.2 (P < 0.01); BNP, 65.7 +/- 1.7 mmHg (P < 0.001)], left atrial pressure (both P < 0.05) (control, 22.0 +/- 0.7; ANP, 19.9 +/- 1.0; BNP, 19.8 +/- 0.9 mmHg) and peripheral resistance [control, 50.3 +/- 4.1 mmHg l-1 min-1; ANP, 46.0 +/- 2.8 (P < 0.05); BNP, 43.8 +/- 4.5 (P < 0.01)], and increased urine volume (2-3-fold, both P < 0.05), sodium excretion (> 10-fold, both P < 0.01) and haematocrit levels relative to control (both P < 0.05). Infused BNP tended to raise plasma ANP levels (by 28 pmol/l), while ANP increased plasma BNP (by 18 pmol/l). Plasma aldosterone was reduced by approximately 40% by both peptides (both P < 0.05). 3. In conclusion, ANP and BNP are both powerfully, natriuretic, similarly suppress aldosterone and appear equipotent in reducing preload and afterload in this model of pacing-induced heart failure.

Human Pro–B-Type Natriuretic Peptide Is Processed in the Circulation in a Rat Model

“…5,2,4,6,8,12,18,25, and 40 min after peptide injections. The samples were immediately placed into tubes containing EDTA (final concentration 5 mmol/L) and the protease inhibitor cocktail (final dilution 1:100) and centrifuged at 1300g for 10 min at 4°C.…”

“…Along with A-and C-type natriuretic peptides, BNP participates in the maintenance of cardiorenal function by increasing sodium excretion and reducing cardiac load and blood pressure (3,4 ). BNP is produced as a 108 -amino acid residue (AAR) precursor molecule, proBNP (5,6 ).…”

Combined Endopeptidase Inhibition and Adrenomedullin in Sheep With Experimental Heart Failure

“…2 On the other hand, NEP inhibition was associated with stable plasma renin and angiotensin II levels (in the face of blood pressure reductions) and a tendency for aldosterone levels to fall, observations consistent with the known renin and aldosterone inhibitory actions of the natriuretic peptides. 3,4 The inhibition of aldosterone by both the natriuretic peptides and ADM may have contributed to their natriuretic/diuretic actions.…”

“…Similarly, augmentation of the natriuretic peptides, via exogenous administration and through prevention of enzymatic degradation by neutral endopeptidase (NEP), has proven to be favorable in the treatment of HF. 3,16,17 The present study was designed to test the hypothesis that combined administration of ADM and an NEP inhibitor will produce additional hemodynamic and renal benefits in HF beyond those achieved by either treatment separately.…”

“…[1][2][3][4] These actions are likely to be beneficial in heart failure (HF), making augmentation of both peptide systems a potential therapeutic strategy. ADM and the natriuretic peptides are activated in HF in proportion to the degree of functional and hemodynamic impairment.…”