Abstract
1 In vitro studies were undertaken on rat aortic strips and portal vein segments to determine whether or not the amine-type anaesthetic, ketamine, can exert direct actions on vascular smooth muscle.
2 Ketamine was found to inhibit development of spontaneous mechanical activity and lower basal tension. This action took place with ketamine concentrations found in anaesthetic plasma concentrations, i.e., 1 × 10-5 to 2 × 10-4 M.
3 Ketamine (10-5 to 10-3 M) dose-dependently attenuated contractions induced by adrenaline, noradrenaline, angiotensin II, vasopressin and KCl. These inhibitory actions were observed with ketamine added either before or after the induced contractions.
4 Ca2+-induced contractions of K+-depolarized aortae and portal veins were also attenuated, dose-dependently, by ketamine.
5 In contrast to the above inhibitory actions, ketamine (2 × 10-6 to 1 × 10-4 M) was found to potentiate specifically 5-hydroxytryptamine(5-HT)-induced contractions of both aortic and venous smooth muscle. However, this was only observed if ketamine was added after 5-HT had initiated a contractile response.
6 All of the inhibitory, as well as 5-HT-potentiating, effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths.
7 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by ketamine.
8 These data suggest that rat plasma concentrations of ketamine commonly associated with induction of surgical anaesthesia can induce, directly, relaxation and contractile potentiation of vascular muscle.
9 These diverse findings may aid in explaining the well-known biphasic pressor actions of ketamine.
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Selected References
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- Adams H. R., Parker J. L., Mathew B. P. The influence of ketamine on inotropic and chronotropic responsiveness of heart muscle. J Pharmacol Exp Ther. 1977 Apr;201(1):171–183. [PubMed] [Google Scholar]
- Altura B. M., Altura B. T. Differential effects of substrate depletion on drug-induced contractions of rabbit aorta. Am J Physiol. 1970 Dec;219(6):1698–1705. doi: 10.1152/ajplegacy.1970.219.6.1698. [DOI] [PubMed] [Google Scholar]
- Altura B. M., Altura B. T. Magnesium and contraction of arterial smooth muscle. Microvasc Res. 1974 Mar;7(2):145–155. doi: 10.1016/0026-2862(74)90001-6. [DOI] [PubMed] [Google Scholar]
- Altura B. M., Edgarian H., Altura B. T. Differential effects of ethanol and mannitol on contraction of arterial smooth muscle. J Pharmacol Exp Ther. 1976 May;197(2):352–361. [PubMed] [Google Scholar]
- Altura B. M. Sex as a factor influencing the responsiveness of arterioles to catecholamines. Eur J Pharmacol. 1972 Dec;20(3):261–265. doi: 10.1016/0014-2999(72)90183-5. [DOI] [PubMed] [Google Scholar]
- Azzaro A. J., Smith D. J. The inhibitory action of ketamine HC1 on [3H]5-hydroxytryptamine accumulation by rat brain synaptosomal-rich fractions: comparison with [3H]catecholamine and [3H]gamma-aminobutyric acid uptake. Neuropharmacology. 1977 May;16(5):349–356. doi: 10.1016/0028-3908(77)90072-7. [DOI] [PubMed] [Google Scholar]
- Bohr D. F. Vascular smooth muscle updated. Circ Res. 1973 Jun;32(6):665–672. doi: 10.1161/01.res.32.6.665. [DOI] [PubMed] [Google Scholar]
- Chang P., Chan K. E., Ganendran A. Cardiovascular effects of 2-(O-chlorophenyl)-2-methylaminocyclohexanone (CI-581) in rats. Br J Anaesth. 1969 May;41(5):391–395. doi: 10.1093/bja/41.5.391. [DOI] [PubMed] [Google Scholar]
- Clanachan A. S., McGrath J. C. Effects of ketamine on the peripheral autonomic nervous system of the rat. Br J Pharmacol. 1976 Oct;58(2):247–252. doi: 10.1111/j.1476-5381.1976.tb10402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clanachan A. S., McGrath J. C., MacKenzie J. E. Cardiovascular effects of ketamine in the pithed rat, rabbit and cat. Br J Anaesth. 1976 Oct;48(10):935–939. doi: 10.1093/bja/48.10.935. [DOI] [PubMed] [Google Scholar]
- Cohen M. L., Chan S. L., Way W. L., Trevor A. J. Distribution in the brain and metabolism of ketamine in the rat after intravenous administration. Anesthesiology. 1973 Oct;39(4):370–376. doi: 10.1097/00000542-197310000-00003. [DOI] [PubMed] [Google Scholar]
- Cohen M. L., Trevor A. J. On the cerebral accumulation of ketamine and the relationship between metabolism of the drug and its pharmacological effects. J Pharmacol Exp Ther. 1974 May;189(2):351–358. [PubMed] [Google Scholar]
- Corssen G., Domino E. F. Dissociative anesthesia: further pharmacologic studies and first clinical experience with the phencyclidine derivative CI-581. Anesth Analg. 1966 Jan-Feb;45(1):29–40. [PubMed] [Google Scholar]
- DOMINO E. F., CHODOFF P., CORSSEN G. PHARMACOLOGIC EFFECTS OF CI-581, A NEW DISSOCIATIVE ANESTHETIC, IN MAN. Clin Pharmacol Ther. 1965 May-Jun;6:279–291. doi: 10.1002/cpt196563279. [DOI] [PubMed] [Google Scholar]
- Dowdy E. G., Kaya K. Studies of the mechanism of cardiovascular responses to CI-581. Anesthesiology. 1968 Sep-Oct;29(5):931–943. doi: 10.1097/00000542-196809000-00014. [DOI] [PubMed] [Google Scholar]
- Edgarian H., Altura B. M. Ethanol and contraction of venous smooth muscle. Anesthesiology. 1976 Apr;44(4):311–317. doi: 10.1097/00000542-197604000-00009. [DOI] [PubMed] [Google Scholar]
- Fuller R. W., Snoddy H. D., Molloy B. B. Blockade of amine depletion by nisoxetine in comparison to other uptake inhibitors. Psychopharmacol Commun. 1975;1(5):455–464. [PubMed] [Google Scholar]
- Godfraind T. Calcium exchange in vascular smooth muscle, action of noradrenaline and lanthanum. J Physiol. 1976 Aug;260(1):21–35. doi: 10.1113/jphysiol.1976.sp011501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Godfraind T., Kaba A. The role of calcium in the action of drugs on vascular smooth muscle. Arch Int Pharmacodyn Ther. 1972 Apr;196(Suppl):–35. [PubMed] [Google Scholar]
- Horwitz L. D. Effects of intravenous anesthetic agents on left ventricular function in dogs. Am J Physiol. 1977 Jan;232(1):H44–H48. doi: 10.1152/ajpheart.1977.232.1.H44. [DOI] [PubMed] [Google Scholar]
- Johnstone M. The cardiovascular effects of ketamine in man. Anaesthesia. 1976 Sep;31(7):873–882. doi: 10.1111/j.1365-2044.1976.tb11898.x. [DOI] [PubMed] [Google Scholar]
- MCCARTHY D. A., CHEN G., KAUMP D. H., ENSOR C. GENERAL ANESTHETIC AND OTHER PHARMACOLOGICAL PROPERTIES OF 2-(O-CHLOROPHENYL)-2-METHYLAMINO CYCLOHEXANONE HCL (CI-58L). J New Drugs. 1965 Jan-Feb;5(1):21–33. doi: 10.1002/j.1552-4604.1965.tb00219.x. [DOI] [PubMed] [Google Scholar]
- McGrath J. C., MacKenzie J. E. The effects of intravenous anaesthetics on the cardiovascular system of the rabbit. Br J Pharmacol. 1977 Oct;61(2):199–212. doi: 10.1111/j.1476-5381.1977.tb08405.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montel H., Starke K., Görlitz B. D., Schümann H. J. Tierexperimentelle Untersuchungen zur Wirkung des Ketamins auf periphere sympathische Nerven. Anaesthesist. 1973 Mar;22(3):111–116. [PubMed] [Google Scholar]
- Nedergaard O. A. Cocaine-like effect of ketamine on vascular adrenergic neurones. Eur J Pharmacol. 1973 Aug;23(2):153–161. doi: 10.1016/0014-2999(73)90051-4. [DOI] [PubMed] [Google Scholar]
- Ochsner A. J., 3rd Cardiovascular and respiratory responses to ketamine hydrochloride in the rhesus monkey (Macaca mulatta). Lab Anim Sci. 1977 Feb;27(1):69–71. [PubMed] [Google Scholar]
- Traber D. L., Wilson R. D. Involvement of the sympathetic nervous system in the pressor response to ketamine. Anesth Analg. 1969 Mar-Apr;48(2):248–252. [PubMed] [Google Scholar]
- Traber D. L., Wilson R. D., Priano L. L. Differentiation of the cardiovascular effects of CI-581. Anesth Analg. 1968 Nov-Dec;47(6):769–778. [PubMed] [Google Scholar]
- Traber D. L., Wilson R. D., Priano L. L. The effect of alpha-adrenergic blockade on the cardiopulmonary response to ketamine. Anesth Analg. 1971 Sep-Oct;50(5):737–742. doi: 10.1213/00000539-197150050-00010. [DOI] [PubMed] [Google Scholar]
- Turlapaty P. D., Altura B. T., Altura B. M. Ethanol reduces Ca2+ concentrations in arterial and venous smooth muscle. Experientia. 1979 May 15;35(5):639–640. doi: 10.1007/BF01960370. [DOI] [PubMed] [Google Scholar]
- Van Breemen C., Farinas B. R., Gerba P., McNaughton E. D. Excitation-contraction coupling in rabbit aorta studied by the lanthanum method for measuring cellular calcium influx. Circ Res. 1972 Jan;30(1):44–54. doi: 10.1161/01.res.30.1.44. [DOI] [PubMed] [Google Scholar]
- Virtue R. W., Alanis J. M., Mori M., Lafargue R. T., Vogel J. H., Metcalf D. R. An anesthetic agent: 2-orthochlorophenyl, 2-methylamino cyclohexanone HCl (CI-581). Anesthesiology. 1967 Sep-Oct;28(5):823–833. doi: 10.1097/00000542-196709000-00008. [DOI] [PubMed] [Google Scholar]
