COMPARATIVE BIOACTIVITY OF ATRIAL AND BRAIN NATRIURETIC PEPTIDES IN AN OVINE MODEL OF HEART-FAILURE

1. Whereas many studies have detailed the effects of exogenous atrial natriuretic peptide (ANP) infusions in heart failure, and a limited nu mber have examined the effects of brain natriuretic peptide (BNP), non e have directly compared the bioactivity of similar doses of ANP and B NP 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 fa ilure (225 beats/min for 8-12 days). 2. Infusion of ANP and BNP increa sed 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) res pectively, in association with cyclic 3',5'-guanosine monophosphate [c ontrol, 40 +/- 6; ANP, 53 +/- 6 (P < 0.05); BNE: 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 pres sure [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) (contro l, 22.0 +/- 0.7; ANP 19.9 +/- 1.0; BNP, 19.8 +/- 0.9 mmHg) and periphe ral 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 v olume (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). Inf used BNP tended to raise plasma ANP levels (by 28 pmol/l), while ANP i ncreased plasma BNP (by 18 pmol/l). Plasma aldosterone was reduced by approximately 40% by both peptides (both Pc 0.05). 3. In conclusion, A NP and BNP are both powerfully natriuretic, similarly suppress aldoste rone and appear equipotent in reducing preload and afterload in this m odel of pacing-induced heart failure.