Linked Life Data

15113846

Source:http://linkedlifedata.com/resource/pubmed/id/15113846

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-8-23
pubmed:abstractText
Daily administration of prednisolone, but not the derivative NCX-1015 (or prednisolone 21-[4'-nitrooxymethyl]benzoate), to rats resulted in a time- and dose-dependent increase in mean arterial blood pressure (MABP), significant after 1 week for the dose of 6.9 micromol/kg i.p. (n = 10; P < 0.05), and 3 weeks for the lower dose of 1.38 micromol/kg. A similar dichotomy of behavior was observed with respect to myocardial contractility and renal vascular resistance, in either case augmented by 3-week treatment with prednisolone but not NCX-1015. In contrast, both NCX-1015 and prednisolone reduced plasma levels of corticosterone in a dose- (dose range of 0.69-6.9 micromol/kg i.p.) and time-dependent (1-3 weeks) manner. Similar profiles were obtained for plasma nitrate values, although they were increased selectively after NCX-1015 administration. In contrast, prednisolone, but not NCX-1015, augmented plasma endothelin 1 (ET-1) with a profile that mirrored the changes observed in MABP and renal blood flow. Supply in the drinking water of the ET-1 receptor type A (ETA) antagonist FR139317 [(R-2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]-carbonyl]amino-4-methylpentanoyl]-amino-3-(2-pyridil)propionic] or mixed ETA/B, but not of selective ETB, antagonists prevented the changes produced by a 21-day treatment with prednisolone. In conclusion, this study indicates 1) a lack of occurrence of cardiovascular alterations by nitro-releasing derivative of prednisolone (NCX-1015), and 2) a functional link between prednisolone effects and the endogenous endothelin-1 system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
310
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1133-41
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The distinct alterations produced in cardiovascular functions by prednisolone and nitro-prednisolone (NCX-1015) in the rat highlight a causal role for endothelin-1.
pubmed:affiliation
The William Harvey Research Institute, Queen Mary School of Medicine and Dentistry, University of London, Charterhouse Square, EC1M 6BQ London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't