[The roles of nitric oxide and prostaglandins in the endotoxin-induced release of calcitonin gene-related peptide (CGRP) in rat mesenteric artery].
The mechanism of endotoxin (ETX) -induced release of CGRP was studied in isolated mesenteric arterial bed. ETX (50 micrograms/ml) caused a 16-fold increase of the release of CGRP. The effect of ETX was enhanced by L-arginine (L-Arg), a substratum of nitric oxide synthase (NOS), by 41%, but inhibited by NG-nitro-L-arginine (L-NNA), an selective inhibitor of NOS, L-NNA, and methylium blue (MB), an inhibitor of guanylate cyclase, respectively by 35% and 36%. These observations suggested that the effect of ETX is, at least partially, mediated by elevation of intracellular cGMP induced by NO. When endothelial cells were removed, the above responses of L-NNA and L-Arg still existed, indicating that ETX activated neuronal, rather than endothelial, NOS. Indomethacin and ibupofen, inhibitors of cyclooxygenase, also inhibited ETX-induced CGRP release by 34% and 39% respectively. When L-NNA and indomethacin were both incubated, no additive effects were discernible. The data suggest that ETX triggers CGRP release partially through activation of NOS located in perivascular sensory nerve and increase of NO, which is followed by activation of cyclooxygenase.
Wang
X
X
Third Hospital, Beijing Medical University.
Wu
Z X
ZX
Tang
Y M
YM
Han
Q D
QD
D000818:Animals; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D066298:In Vitro Techniques; D007213:Indomethacin; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012475:Salmonella
D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D009569:Nitric Oxide; D001120:Arginine; D011451:Prostaglandin-Endoperoxide Synthases; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin