Document Detail

Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart.
MedLine Citation:
PMID:  19424280     Owner:  NLM     Status:  MEDLINE    
Cardiac fibrosis is a hallmark of cardiovascular remodeling associated with hypertension. The purpose of this study was to explore the effect and mechanism of soluble guanylate cyclase (sGC) stimulator BAY 41-2272, leading to intracellular cyclic guanosine monophosphate (cGMP) elevation, on the remodeling process induced by pressure overload. Seven-week-old male Wistar rats with hypertension induced by suprarenal aortic constriction (AC) were treated orally with 2 mg kg(-1) day(-1) of BAY 41-2272 for 14 days. BAY 41-2272 had no effects on blood pressure, but decreased AC-induced collagen accumulation in the left ventricle (LV), inhibiting the number of myofibroblasts and gene expressions of transforming growth factor-beta1 and type 1 collagen. In addition, the antifibrotic action of BAY 41-2272 was accompanied by reducing AC-induced angiotensin-converting enzyme (ACE) mRNA and its enzymatic activity, and angiotensin II concentration in LV. In cultured cardiac fibroblasts, BAY 41-2272 inhibited ACE synthesis and myofibroblast transformation, accompanied by elevating the intracellular cGMP concentration. These results suggest that sGC stimulator BAY 41-2272 might be effective to reduce fibrosis in hypertensive heart disease by attenuating angiotensin II generation through myofibroblast transformation.
Hiroyuki Masuyama; Toshihiro Tsuruda; Yoko Sekita; Kinta Hatakeyama; Takuroh Imamura; Johji Kato; Yujiro Asada; Johannes-Peter Stasch; Kazuo Kitamura
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-08
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  32     ISSN:  1348-4214     ISO Abbreviation:  Hypertens. Res.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-06     Completed Date:  2009-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  597-603     Citation Subset:  IM    
Department of Internal Medicine, Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
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MeSH Terms
Blood Pressure / drug effects*
Blotting, Western
Cells, Cultured
Collagen Type I / biosynthesis,  genetics
Constriction, Pathologic
Fibroblasts / pathology
Gene Expression
Guanylate Cyclase / metabolism*
Heart / physiopathology*
Myocardium / enzymology,  pathology
Myocytes, Cardiac / drug effects,  ultrastructure
Organ Size / drug effects,  physiology
Peptidyl-Dipeptidase A / biosynthesis,  genetics
Pyrazoles / pharmacology
Pyridines / pharmacology
Rats, Wistar
Renin-Angiotensin System / drug effects,  physiology
Stimulation, Chemical
Transforming Growth Factor beta1 / biosynthesis,  genetics
Reg. No./Substance:
0/3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; 0/Collagen Type I; 0/Pyrazoles; 0/Pyridines; 0/Transforming Growth Factor beta1; EC A; EC Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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