|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
7
|
|
pubmed:dateCreated |
2009-7-6
|
|
pubmed:abstractText |
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.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
1348-4214
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
32
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
597-603
|
|
pubmed:meshHeading |
pubmed-meshheading:19424280-Animals,
pubmed-meshheading:19424280-Blood Pressure,
pubmed-meshheading:19424280-Blotting, Western,
pubmed-meshheading:19424280-Cells, Cultured,
pubmed-meshheading:19424280-Collagen Type I,
pubmed-meshheading:19424280-Constriction, Pathologic,
pubmed-meshheading:19424280-Fibroblasts,
pubmed-meshheading:19424280-Fibrosis,
pubmed-meshheading:19424280-Gene Expression,
pubmed-meshheading:19424280-Guanylate Cyclase,
pubmed-meshheading:19424280-Heart,
pubmed-meshheading:19424280-Immunohistochemistry,
pubmed-meshheading:19424280-Male,
pubmed-meshheading:19424280-Myocardium,
pubmed-meshheading:19424280-Myocytes, Cardiac,
pubmed-meshheading:19424280-Organ Size,
pubmed-meshheading:19424280-Peptidyl-Dipeptidase A,
pubmed-meshheading:19424280-Pyrazoles,
pubmed-meshheading:19424280-Pyridines,
pubmed-meshheading:19424280-Rats,
pubmed-meshheading:19424280-Rats, Wistar,
pubmed-meshheading:19424280-Renin-Angiotensin System,
pubmed-meshheading:19424280-Stimulation, Chemical,
pubmed-meshheading:19424280-Transforming Growth Factor beta1
|
|
pubmed:year |
2009
|
|
pubmed:articleTitle |
Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart.
|
|
pubmed:affiliation |
Department of Internal Medicine, Circulatory and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
