caa a22 4500 477056172 CHVBK 20180405111347.0 cr unu---uuuuu 170330e19961201xx s 000 0 eng 10.1007/s002280050196 doi (NATIONALLICENCE)springer-10.1007/s002280050196 Neutral endopeptidase 24.11 inhibition may not exhibit beneficial haemodynamic effects in patients with congestive heart failure [Elektronische Daten] [M. Kentsch, W. Otter, C. Drummer, A. Nötges, R. Gerzer, G. Müller-Esch] Objectives: Inhibition of neutral endopeptidase 24.11 (NEP) prevents degradation of plasma atrial natriuretic peptide (ANP), a substance with vasodilatory and natriuretic properties. The aim of the study was to investigate the haemodynamic and endocrine effects of the NEP inhibitor candoxatril in patients with congestive heart failure (CHF). Methods: In a randomized double-blind, parallel group study design, 24 patients with CHF received a 10-day oral drug treatment with candoxatril (25, 100 or 400 mg b.i.d.) or placebo. Invasive haemodynamics and laboratory parameters were measured on days 1 and 10. Results: On the first treatment day, candoxatril produced a dose-dependent increase in plasma cyclic GMP, the second messenger of ANP. At doses of 100 and 400 mg, candoxatril induced an increase (!) in systemic vascular resistance (SVR) and a decrease in cardiac index (CI), which was not observed with placebo and the lower candoxatril dose. Conclusions: Despite significant activation of the ANP system, reflected by a dose-dependent increase in plasma cyclic GMP concentrations, high doses of candoxatril induced systemic vasoconstrictory rather than vasocilatory effects in patients with CHF. Therefore NEP inhibition by candoxatril may not exhibit beneficial haemodynamic effects in CHF. Springer-Verlag Berlin Heidelberg, 1996 Keywords Metalloproteinases nationallicence Antagonists and inhibitors nationallicence Neutral endopeptidase 24.11 nationallicence natriuretic peptides nationallicence atrial nationallicence congestive heart failure nationallicence haemodynamics nationallicence cyclic GMP nationallicence Kentsch M. Department of Internal Medicine, Medizinische Klinik, Klinikum der Hansestadt Stralsund, Postfach 2341, D-18410 Stralsund, Germany, DE aut Otter W. Department of Internal Medicine, Medizinische Klinik, Klinikum der Hansestadt Stralsund, Postfach 2341, D-18410 Stralsund, Germany, DE aut Drummer C. Institute of Aerospace, DLR, Cologne, Germany, DE aut Nötges A. Herz-Kreislauf-Klinik, Bad Bevensen, Germany, DE aut Gerzer R. Institute of Aerospace, DLR, Cologne, Germany, DE aut Müller-Esch G. Department of Internal Medicine, Medizinische Klinik, Klinikum der Hansestadt Stralsund, Postfach 2341, D-18410 Stralsund, Germany, DE aut https://doi.org/10.1007/s002280050196 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050196 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kentsch M. Department of Internal Medicine, Medizinische Klinik, Klinikum der Hansestadt Stralsund, Postfach 2341, D-18410 Stralsund, Germany, DE aut NATIONALLICENCE 700 1- Otter W. Department of Internal Medicine, Medizinische Klinik, Klinikum der Hansestadt Stralsund, Postfach 2341, D-18410 Stralsund, Germany, DE aut NATIONALLICENCE 700 1- Drummer C. Institute of Aerospace, DLR, Cologne, Germany, DE aut NATIONALLICENCE 700 1- Nötges A. Herz-Kreislauf-Klinik, Bad Bevensen, Germany, DE aut NATIONALLICENCE 700 1- Gerzer R. Institute of Aerospace, DLR, Cologne, Germany, DE aut NATIONALLICENCE 700 1- Müller-Esch G. Department of Internal Medicine, Medizinische Klinik, Klinikum der Hansestadt Stralsund, Postfach 2341, D-18410 Stralsund, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer