Iliev, Bogdan

Khadzhynov, Dmytro

Krämer, Stephanie

Loof, Tanja

Mika, Alice

Neumayer, Hans H

Peters, Harm

Wang-Rosenke, Yingrui

BMC Pharmacology

English

PubMed

Yingrui Wang-Rosenke

Dmytro Khadzhynov

Tanja Loof

Stephanie Krämer

Bogdan Iliev

Alice Mika

Hans H Neumayer

Harm Peters

Crossref

BioMed Central
Page 1 of 1
(page number not for citation purposes)
BMC Pharmacology
Open AccessPoster presentation
Stimulation of soluble guanylate cyclase accelerates renal recovery 
following relief of unilateral ureteral obstruction
Yingrui Wang-Rosenke*, Dmytro Khadzhynov, Tanja Loof, 
Stephanie Krämer, Bogdan Iliev, Alice Mika, Hans H Neumayer and 
Harm Peters
Address: Department of Nephrology and Center of Cardiovascular Research, Charité-Universitätsmedizin, Berlin, Germany
Email: Yingrui Wang-Rosenke* - yingrui.wang@charite.de
* Corresponding author    
Background
Unilateral ureteral obstruction (UUO) is characterized by
progressive renal atrophy, tubular apoptosis and tubu-
lointerstitial fibrosis. Pharmacological stimulation of sol-
uble guanylate cyclase (sGC) and subsequent cGMP
production have recently been found to be renoprotec-
tive. In this study, the sGC stimulator BAY 41-8543 was
given to rats after relief of UUO in order to analyze the
effects of enhanced NO/sGC/cGMP signaling on the sub-
sequent renal disease recovery, concerning the renal atro-
phy, tubular apoptosis and tubulointerstitial fibrosis.
Methods
Male Sprague-Dawley rats underwent UUO. After 5 days,
the obstruction was relieved and the rats were randomly
assigned to UUO-Relief and UUO-Relief plus BAY 41-
8543 (10 mg/kg body weight/day). After 7 days of treat-
ment, effects of stimulated sGC/cGMP on plasma cGMP
levels, systolic blood pressure and renal histology were
determined. The symbol * indicates p < 0.05 UUO-Relief
versus UUO-Relief plus BAY 41-8543.
Results
Untreated UUO-Relief rats showed elevation of systolic
blood pressure, marked tubular atrophy, tubular apopto-
sis, tubulointerstitial macrophage infiltration and fibrosis.
Compared to the untreated rats with UUO-Relief, BAY 41-
8543 treatment increased significantly plasma cGMP lev-
els (+104%*). This went along with significant reductions
in systolic blood pressure (UUO-Relief plus BAY 41-8543
vs UUO-Relief: 112 ± 4 vs 145 ± 8 mmHg*), tubular
diameter (-20%*), tubular apoptosis (-67%*) shown in
TUNEL assay, tubulointerstitial macrophage infiltration (-
65%*) and fibrosis (tubulointerstitial volume -38%*,
expansion of matrix proteins -60%*, deposition of colla-
gen IV -52%* and expression of alpha-smooth muscle
actin -69%*).
Conclusion
Stimulation of sGC by Bay 41-8543 significantly increased
cGMP production and precedes the disease resolution fol-
lowing relief of UUO. This involved improvements in
renal atrophy, tubular apoptosis, tubulointerstitial fibro-
sis and macrophage infiltration. The findings suggest that
pharmacological sGC stimulation is an effective approach
to accelerate restoration of renal architecture and function
following relief of ureteral obstruction.
from 4th International Conference of cGMP Generators, Effectors and Therapeutic Implications
Regensburg, Germany. 19–21 June 2009
Published: 11 August 2009
BMC Pharmacology 2009, 9(Suppl 1):P71 doi:10.1186/1471-2210-9-S1-P71
<supplement> <title> <p>4th International Conference of cGMP Generators, Effectors and Therapeutic Implications</p> </title> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1471-2210-9-S1-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2210-9-S1-info.pdf</url> </supplement>
This abstract is available from: http://www.biomedcentral.com/1471-2210/9/S1/P71
© 2009 Wang-Rosenke et al; licensee BioMed Central Ltd. 


Stimulation of soluble guanylate cyclase accelerates renal recovery following relief of unilateral ureteral obstruction

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Stimulation of soluble guanylate cyclase accelerates renal recovery following relief of unilateral ureteral obstruction

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