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European Journal of Heart Failure 1999 1(4):371-377; doi:10.1016/S1388-9842(99)00058-6
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© 1999 European Society of Cardiology

Disruption of the relationship between renin and atrial natriuretic peptide early in the course of ventricular dysfunction

David P. Dutkaa,*, Sundeep Puria, Rachel Stronga and John G.F. Clelandb

a Imperial College of Science, Technology and Medicine, National Heart and Lung Institute (Hammersmith Campus) Du Cane Road, London W12 0NN, UK
b Foundation Chair in Cardiology, University of Hull, Castle Hill Hospital Castle Road, Cottingham, Hull HU16 5JQ, UK

* Corresponding author. Tel.: +44-181-383-3748; fax: +44-181-383-3742. E-mail address: d.dutka{at}ic.ac.uk (D. P. Dutka)


   Abstract

Background: Plasma renin activity is normal in left ventricular dysfunction in the absence of diuretic therapy. In health there is a reciprocal relationship between renin and atrial natriuretic peptide (ANP) but a positive correlation in advanced heart failure. The relationship between renin and ANP in mild left ventricular dysfunction is unknown.

Methods and Results: Patients with left ventricular dysfunction (n = 35, 18 without diuretic therapy) were compared to 20 age-matched healthy subjects. Plasma concentrations of active renin (PARC), ANP and norepinephrine were measured after 20 min rest and 45 min after an infusion of normal saline (10 ml/kg body wt.). Basal plasma ANP was increased in patients with left ventricular dysfunction compared to healthy subjects, whether or not they were receiving diuretics. PARC was similar in healthy controls and patients untreated with diuretics but was increased in diuretic treated patients. After saline loading in healthy subjects PARC fell while ANP rose. Patients with left ventricular dysfunction had a smaller decline in PARC, that did not achieve statistical significance, but had a greater increase in plasma ANP compared to healthy subjects (P < 0.05). The close reciprocal relationship between PARC and ANP observed in healthy subjects before and after saline loading (r = 0.8, P < 0.001 and r = 0.6, P < 0.01) was weakened in those not receiving diuretics (r = 0.4, P < 0.05 and r = 0.24, ns) and lost in those receiving diuretics (r = 0.1 and r = 0.08).

Conclusions: Patients with left ventricular dysfunction have a disturbance of the normal reciprocal relationship between PARC and ANP which antedates diuretic treatment. This should be taken into account when interpreting plasma neuroendocrine measurements in patients with ventricular dysfunction.

Key Words: Heart failure • Renin • ANP • Neuroendocrine activation

Received June 8, 1999; Revised September 10, 1999; Accepted September 20, 1999


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