Clinical Science zyxwvutsrqp ( 1989) zyxwvutsrq 77,605-6 10 zyxwvutsrqpo 605 Cardiac secretion and renal clearance of atrial natriuretic peptide in normal man: effect of salt restriction KRISHNANKUTTY SUDHIR, PETER FRIBERG*, IAN T. MEREDITH, ROBYN L. WOODS, MURRAY D. ESLER zyxwv AND GARRY L. JENNINGS. Clinical Research Unit, Baker Medical Research Institute and Alfred Hospital, Melbourne, Australia (Received 3 1 January/4 May 1989; accepted 23 May 1989) SUMMARY 1. Previous studies of endogenous atrial natriuretic peptide (ANP) in humans have examined changes in plasma levels, rather than regional secretion and clearance of the peptide. Using arterial and selective venous catheterization and sampling, and measurement of regional organ flow, we measured haemodynamics, cardiac secretion of ANP and renal clearance of ANP in six healthy volunteers at rest, on a normal sodium diet. 2. Salt restriction decreases plasma concentrations of ANP. We assessed the contribution of the heart and kidney to this decrease, by measuring cardiac secretion and renal clearance of ANP at the termination of a low salt diet. 3. Twenty-four hour urinary sodium excretion fell on the low salt diet from 163 to 29 mmol/day [standard error of the difference (SED)+ 14, P<0.001]. Body weight decreased on salt restriction from 76.4 to 75.4 kg (SED f 0.33, zyxwvutsrqp P< 0.05). Brachial mean arterial pressure fell by 6% (P< 0.05), but right atrial pressure was unchanged. Renal vein plasma renin activity increased by 56% with sodium restriction (P< 0.0 1 ), whereas arterial ANP con- centrations fell by 39% (P< zyxwvuts 0.05). 4. Coronary sinus ANP levels fell from 417 to 268 pg/ ml (SED+ 74, P< 0.05), whereas renal vein concentrations were unaltered. There was a 47% decrease in cardiac secretion of ANP in the low salt state (P<0.05). Net extraction of ANP across the kidney (about two-thirds) and renal clearance of ANP were unchanged on the low salt diet. Thus decreased plasma ANP with sodium res- triction is due to reduced cardiac secretion. Key words: coronary sinus atrial natriuretic peptide, renal atrial natriuretic peptide extraction, renal vein renin. *Permanent address: Department of Physiology, University of Goteburg, Goteburg, Sweden. Correspondence: Dr G. L. Jennings, Clinical Research Unit, Baker Medical Research Institute, Commercial Road, Prahran, Victoria 3 18 1, Australia. Abbreviations: ANP, atrial natriuretic peptide; GFR, glomerular filtration rate; PAH, p-aminohippurate; PRA, plasma renin activity; SED, standard error of the dif- ference. INTRODUCTION Atrial natriuretic peptide (ANP) is released from the heart in response to atrial stretch [ 1, 21. It has natriuretic [3] and vasodilator [4] properties, and suppresses the renin-aldosterone axis [5]; thus it is regarded as a possible regulator of circulating fluid volume and blood pressure. Plasma levels are the result of both secretion and clearance of the peptide [6]. Since the heart is the source of ANP [7], selective coronary sinus catheterization and sampling can be used to measure the secretion rate of the peptide. The kidney is a major target organ and possesses a number of clearance pathways for A N P it has therefore been proposed as an important site of ANP clearance and metabolism [8,9]. Salt restriction reduces plasma ANP concentrations [lo]. During sodium restriction, various mechanisms such as activation of the sympathetic nervous and the renin-angiotensin systems [ l l , 121 serve to counteract reduced cardiac output, and to maintain arterial blood pressure. In addition, a decrease in ANP could facilitate conservation of sodium, through withdrawal of the natri- uretic and other properties of the peptide. Changes in plasma ANP during salt restriction may be due to altera- tions in either secretion or clearance of the peptide. In this study, we measured cardiac secretion and renal clearance of ANP in six healthy human subjects on a normal sodium diet, and during salt restriction, to assess the contribution of the heart and kidney to the altered plasma levels seen in salt restriction. METHODS Subjects Six normal male human volunteers (mean age 34.7 years, range 25-50 years) were recruited by advertise-