Linked Life Data

21041233

Source:http://linkedlifedata.com/resource/pubmed/id/21041233

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-18
pubmed:abstractText
Nitric oxide (NO) signaling in tumors and endothelial cells regulates vascular permeability and blood flow and therefore influences tumor uptake and response to therapeutic compounds. As delivery and efficacy of chemotherapy is impaired in CNS neoplasms due to a partially intact blood-brain barrier (BBB), we studied the effects of NO released by the short-acting NO donor disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate methanolate (PROLI/NO) on BBB integrity and blood flow in C6 gliomas using [¹?C]-aminoisobutyric acid (AIB) and [¹?C]-iodoantipyrine quantitative autoradiography. PROLI/NO selectively increased intratumoral uptake of [¹?C]AIB and [¹?C]sucrose when given as a 3-minute intracarotid infusion or a 15-minute i.v. infusion (AIB: tumor, K? = 68.7 ± 3.2 vs 24.9 ± 0.9 µL g?¹ min?¹, P < .0001; sucrose, K? = 16.9 ± 0.9 vs 11.5 ± 0.9 µL g?¹ min?¹, P = .0007). This effect was achieved without significant changes in cerebral and tumor blood flow or arterial blood pressure, which indicates that the effect on vascular permeability is independent of changes in vascular tone induced by NO. This effect was mediated by activation of the NO/3',5'-cyclic guanosine monophosphate (cGMP) pathway, as it was blocked by guanylate cyclase inhibition by LY83583 and reproduced by the delivery of 8-bromoguanosine 5'-monophosphate or inhibition of cGMP degradation by the phosphodiesterase inhibitor zaprinast. Inhibition of inducible NO synthase by aminoguanidine or cyclooxygenase inhibition by indometacin or dexamethasone did not reduce the blood-tumor barrier (BTB) response to PROLI/NO. PROLI/NO, and perhaps other NO-donating compounds, can be used to selectively increase BTB permeability in gliomas through the NO/cGMP pathway at doses that do not cause unwanted vasodilatory changes in blood flow and that do not affect the systemic circulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1523-5866
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
203-11
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Differential effects of nitric oxide on blood-brain barrier integrity and cerebral blood flow in intracerebral C6 gliomas.
pubmed:affiliation
Department of Neurosurgery, University Medical Center Freiburg, Breisacher Strasse 64, D-79106 Freiburg, Germany. astrid.weyerbrock@uniklinik-freiburg.de
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural