gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

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Treatment with lercanidipine influences inflammatory markers and ADMA production

Behandlung mit Lercanidipin beeinflußt inflammatortische Marker und die ADMA Produktion

Meeting Abstract (Hypertonie 2003)

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  • presenting/speaker J. Menne - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)
  • J. Park - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)
  • C. Lindschau - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)
  • J. Kielstein - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)
  • D. Müller - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)
  • F. Bahlmann - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)
  • H. Haller - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)
  • D. Fliser - Phenos GmbH, MHH, Franz-Vollhard Klinik (Hannover, Berlin, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP90

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch190.shtml

Published: November 11, 2004

© 2004 Menne et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Introduction

Prevention of target organ damage is a major goal of antihypertensive therapy, and attenuation of vascular micro inflammation and reversal of endothelial dysfunction play a central role in this respect. We have explored the cardiovascular effects of lercanidipine, i.e. a calcium antagonist of the third generation.

Methods

We studied double transgenic rats (TGR) over expressing the human renin and angiotensinogen gene, which develop severe target organ damage within weeks. 20 animals randomly received 2.5 mg/kg/day lercanidipine (lerca.) or vehicle for 3 weeks. In addition, 10 Spraque-Dawley control rats (SDR) received vehicle.

Results

Cumulative mortality in the observational period was 60% in the untreated TGR, whereas no lerca. treated TGR died (p<0.0001). Systolic blood pressure increased from 167±9 to 260±19 mmHg in untreated TGR, from 163±4 mmHg to 215±20 mmHg in lerca. treated TGR, and from 124±4 mmHg to 154±12 mmHg in SD controls. In parallel, albumin excretion rate increased to 1.70±0.16 mg/24h in untreated TGR as compared with 0.81±0.10 mg/24h in lerca. treated TGR (p<0.01 vs. TGR) and SDR (0.24±0.05 mg/24h). We observed significant monocyte infiltration and significantly increased iNOS and fibronectin expression in renal tissue in untreated TGR as compared with SDR. These effects were obliterated by lerca. In addition, blood levels of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) were significantly higher (p<0.05) in untreated TGR (1.09±0.04) as compared with lerca. treated TGR (0.93±0.01 µmol/l) and SDR (0.83±0.032 µmol/l). Moreover, in an ancillary in-vitro experiment administration of lerca. to TNF-alpha stimulated endothelial cells abolished expression of adhesion molecules.

Conclusions

Lercanidipine has significant cardiovascular protective effects. This salutary action is mediated, at least in part, via an anti-inflammatory effect as well as a reduction of increased ADMA blood levels.