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21181115

Source:http://linkedlifedata.com/resource/pubmed/id/21181115

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pubmed-article:21181115pubmed:abstractTextWe have shown that ischaemic preconditioning ameliorates both the local periosteal and the systemic leukocyte activation evoked by limb ischaemia-reperfusion. We hypothesized that the activation of chemosensitive afferent nerves by transient ischaemia contributes to the protective mechanisms of ischaemic preconditioning via a calcitonin gene-related peptide (CGRP)-dependent mechanism. In Sprague-Dawley rats, 60-min complete limb ischaemia was followed by 180 min of reperfusion. In further experiments, the CGRP analogue hCGRP (0.3 ?g kg(-1)) or ischaemic preconditioning (2?×?10-min ischaemia/10-min reperfusion) was applied prior to the ischaemia-reperfusion insult. Ischaemic preconditioning was performed in three subgroups in which animals received the CGRP receptor antagonist CGRP(8-37) (30 ?g kg(-1) h(-1)), the chemosensitive afferent nerve inactivator resiniferatoxin (3?×?15 ?g kg(-1), sc), or vehicle. The effects of CGRP(8-37) and resiniferatoxin on ischaemia-reperfusion without ischaemic preconditioning were also evaluated. In the tibial periosteum of rats, intravital fluorescence microscopy and immunohistochemistry revealed significant attenuations of ischaemia-reperfusion-induced post-ischaemic leukocyte-endothelial interactions (rolling and adherence in the postcapillary venules) and tissue intracellular adhesion molecule expression following ischaemic preconditioning or hCGRP administration. Administration of CGRP(8-37) or pretreatment of animals with resiniferatoxin reversed the anti-inflammatory effects of limb ischaemic preconditioning, but failed to affect the microcirculatory consequences of ischaemia-reperfusion without ischaemic preconditioning. The results suggest that activation of the chemo- (capsaicin-) sensitive afferent nerves is involved in the mechanisms of microcirculatory anti-inflammatory protection provided by limb ischaemic preconditioning. Controlled activation of chemosensitive C-fibres or the CGRP receptors by the induction of ischaemic preconditioning or other means may furnish therapeutic benefit by ameliorating the periosteal microcirculatory consequences of tourniquet ischaemia.lld:pubmed
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pubmed-article:21181115pubmed:year2011lld:pubmed
pubmed-article:21181115pubmed:articleTitleAnti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats.lld:pubmed
pubmed-article:21181115pubmed:affiliationInstitute of Surgical Research, University of Szeged, Pécsi utca 6, 6720, Szeged, Hungary.lld:pubmed
pubmed-article:21181115pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21181115pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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