Journal of Anesthesia

, Volume 10, Issue 1, pp 58–62 | Cite as

Halothane anesthesia suppresses reflex tachycardia caused by calcitonin gene-related peptide in dogs

  • Shohei Takeda
  • Yutaka Inada
  • Kumiko Matsui
  • Teruaki Tomaru
Original Articles


Calcitonin gene-related peptide (CGRP) is known to produce vasodilation, hypotension, and tachycardia. To investigate the interaction between CGRP and anesthetics, the hemodynamic response to infusions of CGRP was studied in dogs anesthetized with halothane or pentobarbital. In halothane-anesthetized dogs given 0.4 μg·kg−1 of CGRP, mean arterial pressure (MAP) did not change significantly. However, there was a significant reduction in systemic vascular resistance (SVR) associated with significant increases in cardiac index (CI) and stroke volume index (SVI). Higher doses (4 and 40 μg·kg−1) of CGRP produced dose-dependent decreases in MAP accompanied by a reduction in SVR. Further, both CI and SVI significantly increased at 4 μg·kg−1 CGRP but remained unchanged at the 40 μg·kg−1 infusion rate. Heart rate (HR) was not increased at all doses but was decreased at 40 μg·kg−1. In pentobarbital-anesthetized dogs, CGRP at doses of 4 μg·kg−1 produced a qualitatively similar cardiovascular responses as that observed in halothane-anesthetized dogs, but with one exception: HR was significantly increased. The results show that the hemodynamic profiles induced by CGRP during halothane or pentobarbital anesthesia are a decrease in MAP accompanied by a reduction in SVR and no consistent alterations in CI. However, CGRP effects on HR showed in a different way. The results also show that HR response differs depending on the anesthetics used: HR increases during pentobarbital anesthesia, while it does not increase during halothane anesthesia.

Key words

CGRP (calcitonin gene-related peptide) Halothane Pentobarbital Systemic hemodynamics 


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  1. 1.
    Hanko J, Hardebo JE, Kåhrström J, Owman C, Sundler F (1985) Calcitonin gene-related peptide is present in mammalian cerebrovascular nerve fibres and dilates pial and peripheral arteries. Neurosci Lett 57:91–95PubMedCrossRefGoogle Scholar
  2. 2.
    Inagaki S, Kito S, Kubota Y, Girgis S, Hillyard CJ, MacIntyre I (1986) Autoradiographic localization of calcitonin gene-related peptide binding sites in human and rat brains. Brain Res 374:287–298PubMedCrossRefGoogle Scholar
  3. 3.
    Mulderry PK, Ghatei MA, Rodrigo J, Allen JM, Rosenfeld MG, Polak JM, Bloom SR (1985) Calcitonin gene-related peptide in cardiovascular tissue of the rat. Neuroscience 14:947–954PubMedCrossRefGoogle Scholar
  4. 4.
    Tshopp FA, Henke H, Petermann JB, Tobler PH, Janzer R, Hökfelt T, Lundberg JM, Cuello C, Fisher JA (1985) Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary. Proc Natl Acad Sci USA 82:248–252CrossRefGoogle Scholar
  5. 5.
    Howden CW, Logue C, Gavin K, Collie L, Rubin PC (1988) Haemodynamic effects of intravenous human calcitonin generelated-peptide in man. Clin Sci 74:413–418PubMedGoogle Scholar
  6. 6.
    Sirén A-L, Feuerstein G (1988) Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat. J Pharmacol Exp Ther 247:69–78PubMedGoogle Scholar
  7. 7.
    Gardiner SM, Compton AM, Bennett T (1989) Regional hemodynamic effects of calcitonin gene-related peptide. Am J Physiol 256 (Regul Integr Comp Physiol 25):R332-R338PubMedGoogle Scholar
  8. 8.
    Okamoto H, Haka S, Kawasaki T, Sato M, Yoshitake J (1992) Effects of CGRP on baroreflex control of heart rate and renal sympathetic nerve activity in rabbits. Am J Physiol 263 (Regul Integr Comp Physiol 32):R874-R879PubMedGoogle Scholar
  9. 9.
    Fisher LA, Kikkawa DO, Rivier JE, Amara SG, Evans RM, Rosenfeld MG, Vale WW, Brown MR (1983) Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide. Nature 305:534–536PubMedCrossRefGoogle Scholar
  10. 10.
    Franco-Cereceda A, Gennari C, Nami R, Agnusdei D, Pernow J, Lundberg JM, Fisher JA (1987) Cardiovascular effects of calcitonin gene-related peptides I and II in man. Cir Res 60:393–397Google Scholar
  11. 11.
    Gennari C, Fisher JA (1985) Cardiovascular action of calcitonin gene-related peptide in humans. Calcif Tissue Int 37:581–584PubMedGoogle Scholar
  12. 12.
    Halliwill JR, Billman GE (1992) Effect of general anesthesia on cardiac vagal tone. Am J Physiol 262 (Heart Circ Physiol 31):H1719-H1724PubMedGoogle Scholar
  13. 13.
    Cox RH, Bagshaw RJ (1980) Effects of anesthesia on carotid sinus reflex control of arterial hemodynamics in the dog. Am J Physiol 239 (Heart Circ Physiol 8):H681-H691PubMedGoogle Scholar
  14. 14.
    Seagard JL, Hopp FA, Donegan JH, Kalbfleisch JH, Kampine JP (1982) Halothane and the carotid sinus reflex: Evidence for multiple sites of action. Anesthesiology 57:191–202PubMedGoogle Scholar
  15. 15.
    Morita K, Kato I, Uzawa T, Hori M, Noda T (1989) Structure-activity relationship of calcitonin gene related peptide. Horm Metabol Res 21 666–668CrossRefGoogle Scholar
  16. 16.
    Goodman EC, Iversen LL (1986) Calcitonin gene-related peptide: Novel neuropeptide. Life Sci 38:2169–2178PubMedCrossRefGoogle Scholar
  17. 17.
    Lappe RW, Slivjak MJ, Todt JA, Wendt RL (1987) Hemodynamic effects of calcitonin gene-related peptide in conscious rats. Regul Pept 19:307–312PubMedCrossRefGoogle Scholar
  18. 18.
    Haass M, Skofitsch G (1985) Cardiovascular effects of calcitonin gene-related peptide in the pithed rat: Comparison with substance P. Life Sci 37:2085–2090PubMedCrossRefGoogle Scholar
  19. 19.
    Wang BC, Bie P, Leadley Jr RJ, Goetz KL (1989) Cardiovascular effects of calcitonin gene-related peptide in conscious dogs. Am J Physiol 257 (Regul Integr Comp Physiol 26):R726-R731PubMedGoogle Scholar
  20. 20.
    Lynch III C, Vogel S, Sperelakis N (1981) Halothane depression of myocardial slow action potentials. Anesthesiology 55:360–368PubMedCrossRefGoogle Scholar
  21. 21.
    Deegan R, He HB, Wood AJJ, Wood M (1991) Effects of anesthesia on norepinephrine kinetics. Comparison of propofol and halothane anesthesia in dogs. Anesthesiology 75:481–488PubMedGoogle Scholar
  22. 22.
    Joyce CD, Prinz RA, Thomas JX, Fiscus RR, Wang X, Djuricin G, Jacobs HK (1990) Calcitonin gene-related peptide increases coronary flow and decreases coronary resistance. J Surg Res 49:435–440PubMedCrossRefGoogle Scholar

Copyright information

© JSA 1996

Authors and Affiliations

  • Shohei Takeda
    • 1
  • Yutaka Inada
    • 1
  • Kumiko Matsui
    • 1
  • Teruaki Tomaru
    • 1
  1. 1.Department of AnesthesiologyShowa University Fujigaoka HospitalYokohamaJapan

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