Linked Life Data

10642298

Source:http://linkedlifedata.com/resource/pubmed/id/10642298

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Pt 2
pubmed:dateCreated
2000-2-7
pubmed:abstractText
The renin-angiotensin system plays a critical role in the control of blood pressure (BP), and its hyperactivity is associated with the development and maintenance of hypertension. Although traditional pharmacological therapies targeted toward the inhibition of the renin-angiotensin system are effective in the control of this disease, they pose significant limitations. We used an antisense gene delivery strategy to circumvent these limitations and established that a single intracardiac administration of angiotensin type 1 receptor antisense (AT(1)R-AS) causes permanent prevention of hypertension in the spontaneously hypertensive rat (SHR), an animal model of primary human hypertension. Our objectives in this study were 2-fold: to determine (1) whether the targeting of angiotensin I-converting enzyme (ACE) mRNA by a similar antisense strategy would prevent the SHR from developing hypertension and (2) whether the antihypertensive phenotype is transmitted to the offspring from the antisense-treated parents. Administration of a retroviral vector containing ACE antisense (LNSV-ACE-AS) caused a modest yet significant attenuation of high BP ( approximately 15+/-2 mm Hg) exclusively in the SHR. This was associated with a complete prevention of cardiac and renovascular pathophysiological alterations that are characteristic of hypertension. Like their parents, the F(1) generation offspring of the LNSV-ACE-AS-treated SHR expressed lower BP, decreased cardiac hypertrophy, and normalization of renal arterial excitation-coupling compared with offspring derived from the LNSV-ACE-tS (truncated sense)-treated SHR. In addition, the endothelial dysfunction commonly observed in the SHR renal arterioles was significantly prevented in both parents and offspring of the LNSV-ACE-AS-treated SHR. Polymerase chain reaction followed by Southern analysis revealed that the ACE-AS was integrated into the SHR genome and transmitted to the offspring. These observations suggest that transmission of ACE-AS by retroviral vector may be responsible for the transference of normotensive phenotypes in the SHR offspring.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0194-911X
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
202-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10642298-Acetylcholine, pubmed-meshheading:10642298-Angiotensins, pubmed-meshheading:10642298-Animals, pubmed-meshheading:10642298-Blood Pressure, pubmed-meshheading:10642298-Bradykinin, pubmed-meshheading:10642298-Cardiomegaly, pubmed-meshheading:10642298-Cell Line, pubmed-meshheading:10642298-Coronary Circulation, pubmed-meshheading:10642298-Dose-Response Relationship, Drug, pubmed-meshheading:10642298-Female, pubmed-meshheading:10642298-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10642298-Gene Therapy, pubmed-meshheading:10642298-Hypertension, pubmed-meshheading:10642298-Male, pubmed-meshheading:10642298-Oligonucleotides, Antisense, pubmed-meshheading:10642298-Peptidyl-Dipeptidase A, pubmed-meshheading:10642298-Phenotype, pubmed-meshheading:10642298-Phenylephrine, pubmed-meshheading:10642298-Rats, pubmed-meshheading:10642298-Rats, Inbred SHR, pubmed-meshheading:10642298-Rats, Inbred WKY, pubmed-meshheading:10642298-Renal Circulation, pubmed-meshheading:10642298-Retroviridae, pubmed-meshheading:10642298-Transgenes, pubmed-meshheading:10642298-Vascular Resistance, pubmed-meshheading:10642298-Vasodilator Agents
pubmed:year
2000
pubmed:articleTitle
Angiotensin I-converting enzyme antisense gene therapy causes permanent antihypertensive effects in the SHR.
pubmed:affiliation
Department of Physiology, College of Medicine, University of Florida, and the University of Florida Brain Institute, Gainesville, FL 32610-0274, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Retracted Publication, Research Support, Non-U.S. Gov't