Linked Life Data

19179646

Source:http://linkedlifedata.com/resource/pubmed/id/19179646

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-4-1
pubmed:abstractText
Na(+)/H(+) exchanger (NHE-1) inhibition was demonstrated to induce the regression of cardiac hypertrophy (CH) in several experimental models and to inhibit mitochondrial death pathway in "in-vitro" experiments. Since recent reports show that NHE-1 inhibition delays the transition from CH to failure, and apoptosis plays a key role in this process, we investigated the effect of chronic treatment with the NHE-1 blocker cariporide on CH and apoptosis in the SHR. One month of cariporide treatment (30 mg x kg(-1) x day(-1)) induced the regression of CH (cardiomyocyte cross-sectional area: 468 +/- 20 vs. 285 +/- 9 microm(2) in untreated and cariporide-treated spontaneously hypertensive rats; P < 0.05). Apoptosis was assessed by TUNEL staining, the expression of Bcl-2, Bax, and activation of caspase-3 and PARP-1 by immunoblot. Cariporide treatment decreased the TUNEL-positive cells, the Bax-to-Bcl-2 ratio (3.16 +/- 0.32 vs. 1.70 +/- 0.17, untreated and cariporide-treated, respectively; P < 0.05); caspase-3 and PARP-1 activation (465 +/- 62 vs. 260 +/- 22 and 2,239 +/- 62 vs. 1,683 +/- 85 AU, untreated and cariporide-treated, respectively; P < 0.05). Angiotensin II, a growth factor and apoptotic stimulus, was used to induce O(2)(-) production that activated the ERK1/2-p90(RSK) pathway, increasing NHE-1 phosphorylation. These effects were prevented by losartan, N-(2-mercaptopropionyl)-glycine, and cariporide. In conclusion, we present data demonstrating that chronic NHE-1 inhibition with cariporide decreases both hypertrophy and apoptosis susceptibility in the spontaneously hypertensive rat heart. The antiapoptotic effect would be the consequence of two different actions of cariporide: the prevention of cytosolic Na(+) and Ca(2+) overload due to the inhibition of the sarcolemmal NHE-1 and a direct mitochondrial effect preventing mitochondrial permeability transition pore opening.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
8750-7587
pubmed:author
pubmed:issnType
Print
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1325-31
pubmed:meshHeading
pubmed-meshheading:19179646-Angiotensin II, pubmed-meshheading:19179646-Animals, pubmed-meshheading:19179646-Anti-Arrhythmia Agents, pubmed-meshheading:19179646-Apoptosis, pubmed-meshheading:19179646-Blotting, Western, pubmed-meshheading:19179646-Cardiomegaly, pubmed-meshheading:19179646-Cell Nucleus, pubmed-meshheading:19179646-Guanidines, pubmed-meshheading:19179646-In Situ Nick-End Labeling, pubmed-meshheading:19179646-Male, pubmed-meshheading:19179646-Mitochondria, Heart, pubmed-meshheading:19179646-Myocardium, pubmed-meshheading:19179646-Myocytes, Cardiac, pubmed-meshheading:19179646-Rats, pubmed-meshheading:19179646-Rats, Inbred SHR, pubmed-meshheading:19179646-Sodium-Hydrogen Antiporter, pubmed-meshheading:19179646-Sulfones, pubmed-meshheading:19179646-Superoxides, pubmed-meshheading:19179646-bcl-2-Associated X Protein
pubmed:year
2009
pubmed:articleTitle
Chronic NHE-1 blockade induces an antiapoptotic effect in the hypertrophied heart.
pubmed:affiliation
Fellow of Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't