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186 Hypertonie 2011 - Poster Hypertonie 2011 - Poster 187
controlled, multicentre registry including 5.000
patients with a 1 year clinical and a 2 year tele-
phonic follow-up. Patients aged ≥ 18 years with
previously uncontrolled hypertension being either
treatment naïve or uncontrolled on antihyper-
tensive monotherapy will be documented given
they are started on azilsartan by the treating
physician or by any ACE inhibitor (ratio 7:3),
serving as an active control group. The princi-
pal research question is to compare both treat-
ment strategies with respect to blood pressure
target achievement free of adverse events lead-
ing to treatment discontinuation. Further questions
relate to blood and pulse pressure reductions,
persistence, efficacy/safety in relation to co-
morbidity and economic considerations. There
are two subgroups of patients which will a) receive
ambulatory blood pressure monitoring (500
patients), or b) monitored by telemetry (200
patients). In these subgroups a number
of further prognostic variables will be assessed
in relation to the medication used.
Prospects: Azilsartan has been demonstrated
to be efficacious and safe in a number of randomized
clinical trials. The hypertension registry
will help to further define its clinical utility
in achieving safe and effective blood pressure
control in real life.
PS 61
A Combination of Lercanidipine and Enalapril
in Daily Practice - Focussing on Blood
Pressure Control and Vascular Surrogate
Endpoints
Scholze J. 1 , Bramlage P. 2 , Trenkwalder P. 3 ,
Kreutz R. 1,4
1Centrum für Innere Medizin, Medizinische
Poliklinik, Charité Campus Mitte, Berlin, Germany,
2Institut für Kardiovaskuläre Pharmakologie
und Epidemiologie, Mahlow, Germany, 3Klinikum Starnberg, Medizinische Klinik, Starnberg,
Germany, 4Institut für Klinische Pharmakologie
und Toxikologie, Charité-Universitätsmedizin
Berlin, Campus Mitte, Berlin, Germany
Background: A fixed dose combination (FDC) of
enalapril and lercanidipine has been shown to
be effective and safe in reducing blood pressure
in randomized clinical trials. We aimed to determine
effectiveness in daily practice.
Methods: Prospective, open-label multicentre
study with a 3 months follow-up at general
practitioners and internists. Patients were
treated with a FDC of 20mg enalapril-maleate
and 10mg lercanidipine-hydrochloride and BP
was determined in the office (OBPM), and by
discretionary self- (SBPM) and ambulatory-
(ABPM) measurements.
Results: 622 patients (mean age 61.3±13.3
years, 54.2% male, considerable co-morbidity),
BP was reduced by -29.2/-14.2 mmHg (OBPM)
from baseline (164.4/95.2 mmHg). Pulse pressure
was reduced by -15.0±16.4 mmHg. Prevalence
of microalbuminuria was reduced from
14.6% at baseline to 6.5% (p< 0.001). SBPM data
were available for 71% of patients and ABPM
for 12%. In the latter patients BP variability
index was significantly reduced compared to
baseline over 24-h (14.2±4.2 vs. 16.3±4.0; p<
0.001) and with night-time ABPM (13.7±4.9 vs.
15.2±4.4; p=0.022). Treatment was associated
with a low incidence of adverse events (3.4%).
Conclusions: The fixed combination of 20 mg
enalapril-maleate and 10 mg lercanidipinehydrochloride
was effective and well tolerated
in clinical practice. It improved vascular surrogate
endpoints including pulse pressure, blood
pressure variability and microalbuminuria.
Genetik, Genomik, Proteomik
PS 62
Soluble Adenylyl Cyclase (sAC)
Transcriptionally Regulates Genes Involved
in Aldosterone Signalling
Herrmann M. 1 , Guske K. 1 , Schmitz B. 2 , Salomon
A. 2,3 , Roosterman D. 1 , Brand S.-M. 2,3 , Brand E. 1
1University Hospital Münster, Molecular Nephrology,
Münster, Germany, 2Medical Faculty of
the Westfalian Wilhelms-University Münster,
Department of Molecular Genetics of Cardiovascular
Disease, Münster, Germany, 3Leibniz- Institute for Arteriosclerosis Research, Münster,
Germany
Introduction: The soluble adenylyl cyclase
(sAC) activates the Na + /K + -ATPase in renal
epithelial collecting duct cells. Nuclear sAC
constitutes a functional complex with cAMP
response element binding protein (CREB), suggesting
a more general role of sAC in overall
gene regulation. We determined the chromatin
binding capacities of sAC at CRE sequences
and its influence on genes, which play a role in
aldosterone signalling.
Material and Methods: In vascular endothelial
cells (EA.hy926) and in human kidney cell lines
(HEK293T; IHKE), we performed Chromation
Immunoprecipitation (ChIP) assay with antibodies
against sAC and CREB. We conducted
transfection with a CRE luciferase reporter
vector, following treatment with sAC inhibitors
and aldosterone. Total RNA of EA.hy926 cells,
which were treated with sAC inhibitors and aldosterone,
was isolated and subsequently analysed
by real-time PCR for expression of genes
involved in aldosterone signalling.
Results: In vivo binding of sAC at CRE motifs
was shown using CRE consensus sequences
in ChIP experiments. Specific pharmacological
inhibition of sAC led to a significant decrease of
transcriptional activity of the CRE control vector
in endothelial and kidney cell lines. Furthermore,
we were able to show the different effects
of sAC on the expression of downstream targets
of aldosterone signalling, e.g. mineralocorticoid
receptor and Na + /K + -ATPase alpha1 and beta1.
Conclusion: sAC has transcriptional trans-acting
properties as it interacts with CRE sites and
potentially influences the expression of genes,
which play a role in aldosterone signalling.
PS 63
Characterization of KIBRA Promoter Portions
in Kidney and Neuroblastoma Cells
Guske K. 1 , Herrmann M. 1 , Schmitz B. 2 ,
Schelleckes M. 1 , Duning K. 1 , Kremerskothen J. 1 ,
Brand S.-M. 2 , Brand E. 1
1University Hospital Münster, Internal Medicine
D, Münster, Germany, 2Medical Faculty of the
Westfalian Wilhelms-University Münster, Department
of Molecular Genetics of Cardiovascular
Disease, Münster, Germany
Introduction: KIBRA, mainly expressed in kidney
and brain tissue, is involved in brain development
and memory formation as a postsynaptic
scaffold protein. In podocytes, it is proposed to
regulate cell motility as a linker between components
of the cytoskeleton and polarity protein
complexes (Duning et al, JASN 2008). In the
current study, we focused on the regulation of
KIBRA gene expression and functional promoter
characterization.
Material and Methods: Serial promoter deletion
constructs were generated by cloning 3627