| Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart. | |
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MedLine Citation:
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PMID: 19424280 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hiroyuki Masuyama; Toshihiro Tsuruda; Yoko Sekita; Kinta Hatakeyama; Takuroh Imamura; Johji Kato; Yujiro Asada; Johannes-Peter Stasch; Kazuo Kitamura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-08 |
Journal Detail:
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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:
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Created Date: 2009-07-06 Completed Date: 2009-12-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9307690 Medline TA: Hypertens Res Country: England |
Other Details:
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Languages: eng Pagination: 597-603 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects* Blotting, Western Cells, Cultured Collagen Type I / biosynthesis, genetics Constriction, Pathologic Fibroblasts / pathology Fibrosis Gene Expression Guanylate Cyclase / metabolism* Heart / physiopathology* Immunohistochemistry Male Myocardium / enzymology, pathology Myocytes, Cardiac / drug effects, ultrastructure Organ Size / drug effects, physiology Peptidyl-Dipeptidase A / biosynthesis, genetics Pyrazoles / pharmacology Pyridines / pharmacology Rats Rats, Wistar Renin-Angiotensin System / drug effects, physiology Stimulation, Chemical Transforming Growth Factor beta1 / biosynthesis, genetics |
| Chemical | |
Reg. No./Substance:
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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 3.4.15.1/Peptidyl-Dipeptidase A; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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