Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-11-17
pubmed:abstractText
Atrial and brain (B-type) natriuretic peptides (ANP and BNP, respectively) are known to exert various cardioprotective effects. For instance, knocking out the expression of ANP, BNP, or their receptor, guanylyl cyclase-A, induces cardiac hypertrophy and/or fibrosis. The cardiac effects of elevated circulating natriuretic peptides are less well understood, however. We therefore compared angiotensin (Ang) II-induced cardiac hypertrophy and fibrosis in BNP-transgenic (Tg) mice, in which circulating BNP levels were elevated by increased secretion from the liver, and their non-Tg littermates. Left ventricular expression of Ang II type 1a receptor was similar in BNP-Tg and non-Tg mice, and there was no significant difference in the elevation of blood pressure elicited by chronic infusion or acute injection of Ang II. Nevertheless, cardiac hypertrophy and fibrosis were significantly diminished in BNP-Tg mice chronically infused with Ang II. In addition, ventricular activation of extracellular signal-regulated kinase (ERK) induced by acute injection of Ang II was also diminished in BNP-Tg mice, as was activation of ERK kinase (MEK). Conversely, expression of mitogen-activated protein kinase phosphatase (MKP) was significantly increased in the ventricles of BNP-Tg mice. Based on these findings, we conclude that elevated circulating BNP exerts cardioprotective effects via inhibition of a ventricular ERK pathway. The mechanism responsible for this inhibition likely involves 1) increased ventricular MKP expression and 2) inhibition of transduction mediators situated upstream of ERK.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Map2k1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase..., http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Natriuretic Peptide, Brain, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1, http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0916-9636
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
847-53
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14621189-Angiotensin II, pubmed-meshheading:14621189-Animals, pubmed-meshheading:14621189-Blood Pressure, pubmed-meshheading:14621189-Fibrosis, pubmed-meshheading:14621189-Gene Expression, pubmed-meshheading:14621189-Hypertrophy, Left Ventricular, pubmed-meshheading:14621189-MAP Kinase Kinase 1, pubmed-meshheading:14621189-MAP Kinase Kinase 2, pubmed-meshheading:14621189-MAP Kinase Signaling System, pubmed-meshheading:14621189-Mice, pubmed-meshheading:14621189-Mice, Transgenic, pubmed-meshheading:14621189-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:14621189-Mitogen-Activated Protein Kinases, pubmed-meshheading:14621189-Myocardium, pubmed-meshheading:14621189-Natriuretic Peptide, Brain, pubmed-meshheading:14621189-Protein-Tyrosine Kinases, pubmed-meshheading:14621189-Proto-Oncogene Proteins c-fos, pubmed-meshheading:14621189-RNA, Messenger, pubmed-meshheading:14621189-Receptor, Angiotensin, Type 1, pubmed-meshheading:14621189-Vasoconstrictor Agents
pubmed:year
2003
pubmed:articleTitle
Angiotensin II-induced ventricular hypertrophy and extracellular signal-regulated kinase activation are suppressed in mice overexpressing brain natriuretic peptide in circulation.
pubmed:affiliation
Department of Medicine and Clinical Science. Kyoto University Graduate School of Medicine, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't