Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats
Abstract 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 mechanism...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Hartmann, Petra [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2010 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag 2010 |
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| Übergeordnetes Werk: |
Enthalten in: Naunyn-Schmiedeberg's archives of pharmacology - Berlin : Springer, 1873, 383(2010), 2 vom: 23. Dez., Seite 179-189 |
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| Übergeordnetes Werk: |
volume:383 ; year:2010 ; number:2 ; day:23 ; month:12 ; pages:179-189 |
| Links: |
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| DOI / URN: |
10.1007/s00210-010-0588-4 |
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| Katalog-ID: |
SPR001955934 |
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| 245 | 1 | 0 | |a Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats |
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| 520 | |a Abstract 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. | ||
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| 650 | 4 | |a Resiniferatoxin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Preconditioning |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Microcirculation |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Intravital fluorescence microscopy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a ICAM-1 |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Varga, Renáta |4 aut | |
| 700 | 1 | |a Zobolyák, Zsuzsanna |4 aut | |
| 700 | 1 | |a Héger, Júlia |4 aut | |
| 700 | 1 | |a Csősz, Blanka |4 aut | |
| 700 | 1 | |a Németh, István |4 aut | |
| 700 | 1 | |a Rázga, Zsolt |4 aut | |
| 700 | 1 | |a Vízler, Csaba |4 aut | |
| 700 | 1 | |a Garab, Dénes |4 aut | |
| 700 | 1 | |a Sántha, Péter |4 aut | |
| 700 | 1 | |a Jancsó, Gábor |4 aut | |
| 700 | 1 | |a Boros, Mihály |4 aut | |
| 700 | 1 | |a Szabó, Andrea |4 aut | |
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10.1007/s00210-010-0588-4 doi (DE-627)SPR001955934 (SPR)s00210-010-0588-4-e DE-627 ger DE-627 rakwb eng Hartmann, Petra verfasserin aut Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2010 Abstract 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. CGRP (dpeaa)DE-He213 Resiniferatoxin (dpeaa)DE-He213 Preconditioning (dpeaa)DE-He213 Microcirculation (dpeaa)DE-He213 Intravital fluorescence microscopy (dpeaa)DE-He213 ICAM-1 (dpeaa)DE-He213 Varga, Renáta aut Zobolyák, Zsuzsanna aut Héger, Júlia aut Csősz, Blanka aut Németh, István aut Rázga, Zsolt aut Vízler, Csaba aut Garab, Dénes aut Sántha, Péter aut Jancsó, Gábor aut Boros, Mihály aut Szabó, Andrea aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 383(2010), 2 vom: 23. Dez., Seite 179-189 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:383 year:2010 number:2 day:23 month:12 pages:179-189 https://dx.doi.org/10.1007/s00210-010-0588-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 383 2010 2 23 12 179-189 |
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10.1007/s00210-010-0588-4 doi (DE-627)SPR001955934 (SPR)s00210-010-0588-4-e DE-627 ger DE-627 rakwb eng Hartmann, Petra verfasserin aut Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2010 Abstract 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. CGRP (dpeaa)DE-He213 Resiniferatoxin (dpeaa)DE-He213 Preconditioning (dpeaa)DE-He213 Microcirculation (dpeaa)DE-He213 Intravital fluorescence microscopy (dpeaa)DE-He213 ICAM-1 (dpeaa)DE-He213 Varga, Renáta aut Zobolyák, Zsuzsanna aut Héger, Júlia aut Csősz, Blanka aut Németh, István aut Rázga, Zsolt aut Vízler, Csaba aut Garab, Dénes aut Sántha, Péter aut Jancsó, Gábor aut Boros, Mihály aut Szabó, Andrea aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 383(2010), 2 vom: 23. Dez., Seite 179-189 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:383 year:2010 number:2 day:23 month:12 pages:179-189 https://dx.doi.org/10.1007/s00210-010-0588-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 383 2010 2 23 12 179-189 |
| allfields_unstemmed |
10.1007/s00210-010-0588-4 doi (DE-627)SPR001955934 (SPR)s00210-010-0588-4-e DE-627 ger DE-627 rakwb eng Hartmann, Petra verfasserin aut Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2010 Abstract 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. CGRP (dpeaa)DE-He213 Resiniferatoxin (dpeaa)DE-He213 Preconditioning (dpeaa)DE-He213 Microcirculation (dpeaa)DE-He213 Intravital fluorescence microscopy (dpeaa)DE-He213 ICAM-1 (dpeaa)DE-He213 Varga, Renáta aut Zobolyák, Zsuzsanna aut Héger, Júlia aut Csősz, Blanka aut Németh, István aut Rázga, Zsolt aut Vízler, Csaba aut Garab, Dénes aut Sántha, Péter aut Jancsó, Gábor aut Boros, Mihály aut Szabó, Andrea aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 383(2010), 2 vom: 23. Dez., Seite 179-189 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:383 year:2010 number:2 day:23 month:12 pages:179-189 https://dx.doi.org/10.1007/s00210-010-0588-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 383 2010 2 23 12 179-189 |
| allfieldsGer |
10.1007/s00210-010-0588-4 doi (DE-627)SPR001955934 (SPR)s00210-010-0588-4-e DE-627 ger DE-627 rakwb eng Hartmann, Petra verfasserin aut Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2010 Abstract 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. CGRP (dpeaa)DE-He213 Resiniferatoxin (dpeaa)DE-He213 Preconditioning (dpeaa)DE-He213 Microcirculation (dpeaa)DE-He213 Intravital fluorescence microscopy (dpeaa)DE-He213 ICAM-1 (dpeaa)DE-He213 Varga, Renáta aut Zobolyák, Zsuzsanna aut Héger, Júlia aut Csősz, Blanka aut Németh, István aut Rázga, Zsolt aut Vízler, Csaba aut Garab, Dénes aut Sántha, Péter aut Jancsó, Gábor aut Boros, Mihály aut Szabó, Andrea aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 383(2010), 2 vom: 23. Dez., Seite 179-189 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:383 year:2010 number:2 day:23 month:12 pages:179-189 https://dx.doi.org/10.1007/s00210-010-0588-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 383 2010 2 23 12 179-189 |
| allfieldsSound |
10.1007/s00210-010-0588-4 doi (DE-627)SPR001955934 (SPR)s00210-010-0588-4-e DE-627 ger DE-627 rakwb eng Hartmann, Petra verfasserin aut Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats 2010 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2010 Abstract 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. CGRP (dpeaa)DE-He213 Resiniferatoxin (dpeaa)DE-He213 Preconditioning (dpeaa)DE-He213 Microcirculation (dpeaa)DE-He213 Intravital fluorescence microscopy (dpeaa)DE-He213 ICAM-1 (dpeaa)DE-He213 Varga, Renáta aut Zobolyák, Zsuzsanna aut Héger, Júlia aut Csősz, Blanka aut Németh, István aut Rázga, Zsolt aut Vízler, Csaba aut Garab, Dénes aut Sántha, Péter aut Jancsó, Gábor aut Boros, Mihály aut Szabó, Andrea aut Enthalten in Naunyn-Schmiedeberg's archives of pharmacology Berlin : Springer, 1873 383(2010), 2 vom: 23. Dez., Seite 179-189 (DE-627)254638309 (DE-600)1462940-9 1432-1912 nnns volume:383 year:2010 number:2 day:23 month:12 pages:179-189 https://dx.doi.org/10.1007/s00210-010-0588-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 383 2010 2 23 12 179-189 |
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English |
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Enthalten in Naunyn-Schmiedeberg's archives of pharmacology 383(2010), 2 vom: 23. Dez., Seite 179-189 volume:383 year:2010 number:2 day:23 month:12 pages:179-189 |
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Enthalten in Naunyn-Schmiedeberg's archives of pharmacology 383(2010), 2 vom: 23. Dez., Seite 179-189 volume:383 year:2010 number:2 day:23 month:12 pages:179-189 |
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CGRP Resiniferatoxin Preconditioning Microcirculation Intravital fluorescence microscopy ICAM-1 |
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Hartmann, Petra @@aut@@ Varga, Renáta @@aut@@ Zobolyák, Zsuzsanna @@aut@@ Héger, Júlia @@aut@@ Csősz, Blanka @@aut@@ Németh, István @@aut@@ Rázga, Zsolt @@aut@@ Vízler, Csaba @@aut@@ Garab, Dénes @@aut@@ Sántha, Péter @@aut@@ Jancsó, Gábor @@aut@@ Boros, Mihály @@aut@@ Szabó, Andrea @@aut@@ |
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2010-12-23T00:00:00Z |
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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. 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Hartmann, Petra |
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Hartmann, Petra misc CGRP misc Resiniferatoxin misc Preconditioning misc Microcirculation misc Intravital fluorescence microscopy misc ICAM-1 Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats |
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Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats CGRP (dpeaa)DE-He213 Resiniferatoxin (dpeaa)DE-He213 Preconditioning (dpeaa)DE-He213 Microcirculation (dpeaa)DE-He213 Intravital fluorescence microscopy (dpeaa)DE-He213 ICAM-1 (dpeaa)DE-He213 |
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misc CGRP misc Resiniferatoxin misc Preconditioning misc Microcirculation misc Intravital fluorescence microscopy misc ICAM-1 |
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Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats |
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Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats |
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Hartmann, Petra Varga, Renáta Zobolyák, Zsuzsanna Héger, Júlia Csősz, Blanka Németh, István Rázga, Zsolt Vízler, Csaba Garab, Dénes Sántha, Péter Jancsó, Gábor Boros, Mihály Szabó, Andrea |
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10.1007/s00210-010-0588-4 |
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anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats |
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Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats |
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Abstract 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. © Springer-Verlag 2010 |
| abstractGer |
Abstract 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. © Springer-Verlag 2010 |
| abstract_unstemmed |
Abstract 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. © Springer-Verlag 2010 |
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| score |
7.399088 |