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Clinical Science (2003) 104, (429–436) (Printed in Great Britain)

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Natriuretic peptides maintain sodium homoeostasis during chronic volume loading post-myocardial infarction in sheep

Christopher J. CHARLES, John M. ELLIOTT, M. Gary NICHOLLS, Miriam T. RADEMAKER and A. Mark RICHARDS

Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand

Key words: experimental myocardial infarction, haemodynamics, heart, heart failure, natriuretic peptide, sodium homoeostasis.

Abbreviations: ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; HF, heart failure; i.v., intravenous; LAD, left anterior descending coronary artery; LV, left ventricular; LVD, LV dysfunction; LVEF, LV ejection fraction; MAP, mean arterial pressure; MI, myocardial infarction; NT-BNP, N-terminal fragment of pro-BNP; PRA, plasma renin activity; RAAS, renin–angiotensin–aldosterone system; RAP, right atrial pressure; TIVCC, thoracic inferior vena caval constriction.

Correspondence: Dr C.J. Charles (e-mail chris.charles@chmeds.ac.nz).

The impaired ability to excrete sodium is a key feature of established congestive heart failure and is also apparent in asymptomatic left ventricular (LV) impairment. However, few studies have examined responses to chronic volume loading immediately post-myocardial infarction (MI). Experimental MI was induced in six sheep by thrombogenic coil coronary artery occlusion, and resulted in significant LV dysfunction with reduced LV ejection fraction (P = 0.001) and subsequent remodelling (increased LV volumes, P = 0.015). Chronic volume loading with 2, 3 and 4litres/day intravenous saline (each for 7 days) showed no evidence of renal sodium or volume retention in sheep with experimental MI compared with six normal control sheep. Plasma levels of brain natriuretic peptide (BNP), N-terminal pro-BNP and cGMP (all P<0.05) were higher in the MI group compared with normal control sheep. There were no differences in haemodynamics, body mass or renin–aldosterone levels between groups. This study provides evidence that natriuretic peptides play a pivotal role in preserving volume/electrolyte balance in the early stages of post-MI cardiac dysfunction.

Received 11 September 2002/19 November 2002; accepted 29 January 2003

The Biochemical Society and the Medical Research Society © 2003