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 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.
Rademaker
M T
MT
Department of Medicine, Christchurch School of Medicine, New Zealand.
Charles
C J
CJ
Espiner
E A
EA
Frampton
C M
CM
Nicholls
M G
MG
Richards
A M
AM
D000450:Aldosterone / Q000097:blood; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006333:Heart Failure / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood / Q000493:pharmacokinetics*; D012756:Sheep; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium