Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1990-12-28
pubmed:abstractText
One component of cyclosporin A (CsA) nephrotoxicity is thromboxane (Tx) A2 induced renal vasoconstriction. This study was designed to investigate whether coadministration of angiotensin converting enzyme inhibitors (ACEI) and thromboxane synthetase inhibition (TSI) could act synergistically to improve the glomerular filtration rate in CsA treated animals. CsA administration (50 mg/kg/day p.o.) to Sprague-Dawley rats for 14 days caused a significant decline in creatinine clearance (CCR), an increase in N-acetyl-beta-D-glucosaminidase (NAG) enzymuria and renal tubulointerstitial damage. These changes were associated with a ten-fold increase in urinary TxB2 excretion (from pretreatment values of 17.2 +/- 6.0 ng/day to 174.9 +/- 65.4 ng/day on day 14). Treatment with TSI normalized TxB2 excretion; this was associated with partial protection against CsA induced changes in CCR and NAG enzymuria and the complete prevention of acute proximal tubular vacuolation. However, the coadministration of both TSI and ACEI removed the protective effects exerted by TSI alone and resulted in elevated urinary TxB2 levels similar to those observed in other CsA treated groups. Treatment with ACEI alone did not affect CsA nephrotoxicity. We suggest that elevated TxB2 synthesis is in part responsible for some aspects of renal functional and morphological damage, but that CsA nephrotoxicity is multifactorial and may result from direct cellular toxicity in addition to vascular changes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2323-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Effect of thromboxane synthetase inhibition and angiotensin converting enzyme inhibition on acute cyclosporin A nephrotoxicity.
pubmed:affiliation
Department of Medicine & Therapeutics, University of Aberdeen, U.K.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't