Linked Life Data

10027844

Source:http://linkedlifedata.com/resource/pubmed/id/10027844

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-4-1
pubmed:abstractText
A genetic alteration in the adducin genes is associated with hypertension and up-regulation of the expression of renal Na, K-ATPase in Milan-hypertensive (MHS) rats, in which increased ouabain-like factor (OLF) levels are also observed. PST 2238, a new antihypertensive compound that antagonizes the pressor effect of ouabain in vivo and normalizes ouabain-dependent up-regulation of the renal Na-K pump, was evaluated for its ability to lower blood pressure and regulate renal Na,K-ATPase activity in MHS genetic hypertension. In this study, we show that PST 2238, given orally at very low doses (1 and 10 microg/kg for 5-6 weeks), reduced the development of hypertension in MHS rats and normalized the increased renal Na,K-ATPase activity and mRNA levels, whereas it did not affect either blood pressure or Na,K-ATPase in Milan-normotensive (MNS) rats. In addition, a similar antihypertensive effect was observed in adult MHS rats after a short-term treatment. In cultured rat renal cells with increased Na-K pump activity at Vmax due to overexpression of the hypertensive variant of adducin, 5 days of incubation with PST 2238 (10(-10-)-10(-9) M) lowered the pump rate to the level of normal wild-type cells, which in turn were not affected by the drug. In conclusion, PST 2238 is a very potent compound that in MHS rats reduces blood pressure and normalizes Na-K pump alterations caused by a genetic alteration of the cytoskeletal adducin. Because adducin gene mutations have been associated with human essential hypertension, it is suggested that PST 2238 may display greater antihypertensive activity in those patients carrying such a genetic alteration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1074-83
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10027844-Androstanols, pubmed-meshheading:10027844-Animals, pubmed-meshheading:10027844-Antihypertensive Agents, pubmed-meshheading:10027844-Blood Pressure, pubmed-meshheading:10027844-Calmodulin-Binding Proteins, pubmed-meshheading:10027844-Cells, Cultured, pubmed-meshheading:10027844-Down-Regulation, pubmed-meshheading:10027844-Enzyme Inhibitors, pubmed-meshheading:10027844-Heart Rate, pubmed-meshheading:10027844-Hypertension, pubmed-meshheading:10027844-Kidney Medulla, pubmed-meshheading:10027844-Male, pubmed-meshheading:10027844-Mutation, pubmed-meshheading:10027844-Ouabain, pubmed-meshheading:10027844-RNA, Messenger, pubmed-meshheading:10027844-Rats, pubmed-meshheading:10027844-Rats, Inbred SHR, pubmed-meshheading:10027844-Rats, Inbred Strains, pubmed-meshheading:10027844-Sodium-Potassium-Exchanging ATPase, pubmed-meshheading:10027844-Transfection
pubmed:year
1999
pubmed:articleTitle
PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension.
pubmed:affiliation
Prassis Research Institute Sigma-Tau, Milan, Italy. pstbio@tin.it
pubmed:publicationType
Journal Article, Comparative Study