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CLINICAL STUDIES

Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study

Andreas Luchner, MD^a, John C. Burnett, Jr., MD^*, Michihisa Jougasaki, MD, PhD^*, Hans-Werner Hense, MD , G.ünter A. J. Riegger, MD^a and Heribert Schunkert, MD^a

^a Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany
^* Cardiorenal Research Laboratory, Mayo Clinic, Rochester, Minnesota, USA
GSF-Institut für Epidemiologie, Munich, Germany
Institut für Epidemiologie und Sozialmedizin, University of Münster, Münster, Germany

Manuscript received January 14, 1998; revised manuscript received July 24, 1998, accepted August 20, 1998.

Address for correspondence: Dr. Heribert Schunkert, Klinik und Poliklinik für Innere Medizin II, University of Regensburg, D-93042 Regensburg, Germany
heribert.schunkert{at}klinik.uni-regensburg.de

Objectives. The present retrospective analysis of data derived from a population-based study examined the relationship between intake of beta-receptor antagonists and plasma concentrations of the cardiac natriuretic peptides and their second messenger.

Background. Beta-receptor antagonists are widely used for treatment of cardiovascular disease. In addition to direct effects on heart rate and cardiac contractility, recent evidence suggests that beta-receptor antagonists may also modulate the cross talk between the sympathetic nervous system and the cardiac natriuretic peptide system.

Methods. Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their second messenger cyclic guanosine monophosphate (cGMP) were assessed in addition to anthropometric, hemodynamic and echocardiographic parameters in a population-based sample (n = 672), of which 80 subjects used beta-receptor antagonists.

Results. Compared to subjects without medication, subjects receiving beta-receptor antagonists were characterized by substantially elevated ANP, BNP and cGMP plasma concentrations (plus 32%, 89% and 18%, respectively, p < 0.01 each). Analysis of subgroups revealed that this effect was highly consistent and present even in the absence of hypertension, left atrial enlargement, left ventricular hypertrophy or left ventricular dysfunction. The most prominent increase was observed in a subgroup with increased left ventricular mass index. By multivariate analysis, a statistically significant and independent association between beta-receptor antagonism and ANP, BNP and cGMP concentrations was confirmed. Such an association could not be demonstrated for other antihypertensive agents such as angiotensin-converting enzyme inhibitors or diuretics.

Conclusions. Beta-receptor antagonists appear to augment plasma ANP, BNP and cGMP concentrations. The current observation suggests an important contribution of the cardiac natriuretic peptide system to the therapeutic mechanism of beta-receptor antagonists.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme inhibition   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   cGMP = cyclic guanosine monophosphate   EDD = end diastolic diameter   FS = fractional shortening   LVM = left ventricular mass   LVMI = left ventricular mass index

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