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Local neurogenic regulation of rat hindlimb circulation: CO 2 ‐induced release of calcitonin gene‐related peptide from sensory nerves
Author(s) -
Yamada Masami,
Ishikawa Tomohisa,
Yamanaka Akihiro,
Fujimori Akira,
Goto Katsutoshi
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701423
Subject(s) - calcitonin gene related peptide , hindlimb , endocrinology , medicine , chemistry , stimulation , calcitonin , sensory nerve , capsaicin , bolus (digestion) , vasodilation , perfusion , receptor , neuropeptide , biology , sensory system , neuroscience
1 The mechanism of release of calcitonin gene‐related peptide (CGRP) from sensory nerves in response to skeletal muscle contraction was investigated in the rat hindlimb in vivo and in vitro . 2 In the anaesthetized rat, sciatic nerve stimulation at 10 Hz for 1 min caused a hyperaemic response in the hindlimb. During the response, partial pressure of CO 2 in the venous blood effluent from the hindlimb significantly increased from 43±3 to 73±8 mmHg, whereas a small decrease in pH and no appreciable change in partial pressure of O 2 were observed. 3 An intra‐arterial bolus injection of NaHCO 3 (titrated to pH 7.2 with HCl), which elevated P CO 2 of the venous blood, caused a sustained increase in regional blood flow of the iliac artery. Capsaicin (0.33 μmol kg −1 , i.a.) and a specific calcitonin gene‐related peptide (CGRP) receptor antagonist, CGRP(8–37), (100 nmol kg −1 min −1 , i.v.) significantly suppressed the hyperaemic response to NaHCO 3 . Neither ND Ω ‐nitro‐ L ‐arginine methyl ester (1 μmol kg −1 min −1 , i.v.) nor indomethacin (5 mg kg −1 , i.v.) affected the response. 4 The serum level of CGRP‐like immunoreactivity in the venous blood was significantly increased by a bolus injection of NaHCO 3 (pH=7.2) from 50±4 to 196±16 fmol ml −1 . 5 In the isolated hindlimb perfused with Krebs‐Ringer solution, a bolus injection of NaHCO 3 (pH=7.2) caused a decrease in perfusion pressure which was composed of two responses, i.e., an initial transient response and a slowly‐developing long‐lasting one. CGRP(8–37) significantly inhibited the latter response by 73%. 6 These results suggest that CO 2 liberated from exercising skeletal muscle activates capsaicin‐sensitive perivascular sensory nerves locally, which results in the release of CGRP from their peripheral endings, and then the released peptide causes local vasodilatation.British Journal of Pharmacology (1997) 122 , 710–714; doi: 10.1038/sj.bjp.0701423