Brain natriuretic peptide: natriuretic and endocrine effects in essential hypertension

Abstract

Objective: Documentation of the renal, hormonal and haemodynamic effects and plasma clearance of human brain natriuretic peptide (BNP) given (in a dose inducing increases in plasma BNP concentrations to pathophysiological levels) to patients with essential hypertension.

Design: Six male patients with untreated, uncomplicated, mild-to-moderate essential hypertension underwent placebo-controlled single-blind studies in balanced random order. Human BNP (2 pmol/kg per min) and vehicle were given as constant intravenous infusions in a volume of 15 ml/h for 2 h. Continuous recording of intra-arterial blood pressure and heart rate, together with serial blood samples (for hormone assays) and 30-min urine collections, were obtained throughout the studies from 90 min before commencement of infusions to 90 min after completion of infusions.

Results: Achieved intra-infusion plasma BNP immunoreactivity (20-30 pmol/l) was similar to levels previously observed in heart failure. Plasma cyclic GMP was increased. Sodium excretion rose to 2.5-fold placebo values. Plasma aldosterone fell to 50% of placebo values. Blood pressure and heart rate were unchanged. The metabolic clearance rate (5.0 +/- 0.4 l/min) and plasma half-life (19.5 min) indicated that BNP has a large volume of distribution (141 +/- 16 litre).

Conclusions: In essential hypertension pathophysiological plasma concentrations of human BNP have significant acute effects promoting natriuresis and suppressing plasma aldosterone. These effects are similar to those of ANP, but the plasma half-life and volume of distribution of BNP are considerably greater than those of atrial natriuretic peptide. These two hormones may play separate complementary roles in fluid volume and blood pressure homeostasis.