Linked Life Data

19536069

Source:http://linkedlifedata.com/resource/pubmed/id/19536069

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-9-30
pubmed:abstractText
Angiotensin II receptor blockers (ARBs) have a potent ability to inhibit oxidative stress and advanced glycation, in addition to their protective effects originated from blood pressure lowering and angiotensin II type 1 receptor (AT(1))-blockade. To obtain a pharmacological tool to dissect the mechanisms of ARBs' protective benefits in experimental stroke, we synthesized a novel ARB-derivative, R-147176, which is 6,700 times less potent than olmesartan in AT(1)-binding inhibition and therefore has a minimal antihypertensive effect, but retains marked inhibitory effects on oxidative stress and advanced glycation. We evaluated the effect of R-147176 (10-30 mg/kg per day), administered orally or intravenously, on brain infarct volume in transient thread occlusion and photothrombotic models in rats. The antioxidative and antiinflammatory properties were also investigated. R-147176 significantly reduced infarct volume, without influence on blood pressure, in both models. R-147176 significantly reduced the numbers of ED-1-positive cells and of TUNEL-positive cells, and protein carbonyl formation in the damaged brain. This ARB derivative, despite its significantly lower AT1 affinity and virtually no antihypertensive effect, ameliorated ischemic cerebral damage through antioxidative and antiinflammatory properties. These findings suggest potential usefulness of R-147176 as a pharmacological tool to investigate the ARBs' protective effect in experimental stroke and open new therapeutic avenues.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1559-7016
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1665-72
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19536069-Angiotensin II Type 1 Receptor Blockers, pubmed-meshheading:19536069-Angiotensin Receptor Antagonists, pubmed-meshheading:19536069-Animals, pubmed-meshheading:19536069-Anti-Inflammatory Agents, pubmed-meshheading:19536069-Antioxidants, pubmed-meshheading:19536069-Brain Ischemia, pubmed-meshheading:19536069-Drug Evaluation, Preclinical, pubmed-meshheading:19536069-Glycosylation End Products, Advanced, pubmed-meshheading:19536069-Hypertension, pubmed-meshheading:19536069-Imidazoles, pubmed-meshheading:19536069-Male, pubmed-meshheading:19536069-Oxidative Stress, pubmed-meshheading:19536069-Protein Binding, pubmed-meshheading:19536069-Rats, pubmed-meshheading:19536069-Rats, Sprague-Dawley, pubmed-meshheading:19536069-Receptors, Angiotensin, pubmed-meshheading:19536069-Thiazolidinediones
pubmed:year
2009
pubmed:articleTitle
A sartan derivative with a very low angiotensin II receptor affinity ameliorates ischemic cerebral damage.
pubmed:affiliation
Division of Neurology, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't