Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats
| Autor: | Blanka Csősz, István Németh, Péter Sántha, Andrea Szabó, Petra Hartmann, Renáta Varga, Zsuzsanna Zobolyák, Csaba Vizler, Mihály Boros, Zsolt Rázga, Gábor Jancsó, Júlia Héger, Dénes Garab |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Sensory Receptor Cells Calcitonin Gene-Related Peptide Resiniferatoxin Ischemia Calcitonin gene-related peptide Pharmacology Microcirculation Rats Sprague-Dawley chemistry.chemical_compound Nerve Fibers Venules Calcitonin Gene-Related Peptide Receptor Antagonists Periosteum medicine Cell Adhesion Leukocytes Animals Humans Leukocyte Rolling Neurons Afferent Ischemic Preconditioning ICAM-1 Microscopy Video Antagonist General Medicine medicine.disease Intercellular Adhesion Molecule-1 Peptide Fragments Hindlimb Rats medicine.anatomical_structure chemistry Capsaicin Anesthesia Reperfusion Injury Diterpenes Sensory nerve Receptors Calcitonin Gene-Related Peptide |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 383(2) |
| ISSN: | 1432-1912 |
| Popis: | We 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 μg 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 μg kg(-1) h(-1)), the chemosensitive afferent nerve inactivator resiniferatoxin (3 × 15 μg 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. |
| Databáze: | OpenAIRE |
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