[Endotoxin causes release of calcitonin gene-related peptide (CGRP) from the isolated mesenteric arterial bed in rat]

Abstract

Our previous work has shown that CGRP is released into the circulation during endotoxin or hemorrhagic shock in animals and septic shock in patients. We have also identified the blood vessels as a major source of production of circulating CGRP in the endotoxic rat. In the present study we determined whether ETX could directly trigger release of CGRP from CGRP-containing perivascular nerves in isolated mesenteric arterial bed (MAB) of rat. The results showed that ETX caused time- and concentration (10-100 micrograms/ml) -dependent release of CGRP. ETX (50 micrograms/ml) is increased by 20 fold CGRP in perfusate 10-15 min after ETX. Characterization of CGRP in perfusates by reverse-phase HPLC showed one predominant peak which coeluted with synthetic rat CGRP. Pretreated MAB with capsaicin or ruthenium red inhibited ETX-induced release of CGRP by 90% and 65% respectively. ETX-induced CGRP release was decreased under Ca2+-free perfusion by 80%. The data suggest that ETX directly trigger the release of CGRP from capsaicin-sensitive sensory nerve innervating blood vessels. The release of CGRP is dependent on extra-cellular Ca2+ and Ca2+-induced Ca2+ release from the intracellular Ca2+ store which is sensitive to ruthenium red.