The effects of volatile anesthetics on nonadrenergic, noncholinergic depressor responses in rats.
The effects of volatile anesthetics on nonadrenergic, noncholinergic (NANC) transmission mediated by calcitonin gene-related peptide (CGRP) are unclear. We studied the effects of isoflurane, halothane, and sevoflurane on NANC depressor responses to electrical spinal cord stimulation in pithed rats whose mean arterial blood pressure was maintained near 120 mm Hg by continuous infusion of methoxamine. Autonomic outflow was blocked by hexamethonium. After 30 min of inhalation of different concentrations of anesthetics, spinal cord stimulation at the lower thoracic level (10 V at 4 Hz; duration, 1 ms) was applied for 30 s to induce a NANC depressor response. Isoflurane at 2% and halothane at 1.5% attenuated NANC depressor responses significantly, whereas isoflurane at 1%, halothane at 0.75%, and sevoflurane at 2% or 4% did not. Volatile anesthetics did not attenuate the release of CGRP after spinal cord stimulation, whereas isoflurane at 2% and halothane at 1.5% significantly inhibited depressor responses to exogenously administered CGRP. Sevoflurane at 4% did not significantly affect CGRP-induced depressor responses. Thus, isoflurane and halothane at large concentrations attenuate NANC depressor responses by attenuating the depressor action of CGRP, not CGRP release.


CONCLUSIONS
The anesthetics isoflurane and halothane attenuate nonadrenergic, noncholinergic depressor responses mediated by calcitonin gene-related peptide in the rat without affecting the release of the peptide.
Yoshikawa
Daisuke
D
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, Maebashi, Japan. yosikawa@med.gunma-u.ac.jp
Kuroda
Masataka
M
Tsukagoshi
Hiroshi
H
Takahashi
Ken-Ichiro
K
Saito
Shigeru
S
Nishikawa
Koichi
K
Goto
Fumio
F
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D003655:Decerebrate State / Q000503:physiopathology; D004558:Electric Stimulation; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008738:Methyl Ethers / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D013116:Spinal Cord / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D014662:Vasoconstrictor Agents; D000077149:Sevoflurane; D007530:Isoflurane; D008729:Methoxamine; D015740:Calcitonin Gene-Related Peptide; D006221:Halothane