Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-12-01T00:27:21.217Z Has data issue: false hasContentIssue false

Effects of the α2-adrenoceptor agonist, guanfacine, on growth rate, glucose, corticosterone, insulin and energy partitioning in rats

Published online by Cambridge University Press:  18 August 2016

C. Gazzola*
Affiliation:
Agency for Food and Fibre Sciences, PO Box 5545, Rockhampton, Queensland 4702, Australia
W. G. Spiers
Affiliation:
CSIRO Livestock Industries, PO Box 5545, Rockhampton, Queensland 4702, Australia Current address: 4 Ryan Street, Zilzie, Queensland 4700, Australia
Get access

Abstract

In experiment 1, female Wistar rats (no. = 24) with free access to food were treated daily for 8 days with subcutaneous injections of saline or 0·5 mg/kg of the α2-adrenoceptor agonist, guanfacine hydrochloride. In experiment 2, female Wistar rats (no. = 24), restricted to 12 g food per day were treated daily for 45 days with subcutaneous injections of 1 μl/g body weight saline containing 0, 0.001, 0.025 or 0·5 mg/kg guanfacine hydrochloride. In experiment 1, the control and treated groups consumed similar amounts of food but the guanfacine-treated animals gained less body weight (P 0.05) and less muscle mass (P 0.01). The treated animals had pronounced glucosuria (P < 0.05) during the whole treatment period. At slaughter, the treated group had higher blood glucose (P < 0.001) and serum corticosterone (P < 005) but insulin concentrations were not different. In experiment 2, only the 0.5 mg/kg dose of guanfacine had significant effects. Resting oxygen consumption on day 29 of treatment was proportionately 0.10 lower in this group compared with controls (P < 0.05). There was no effect of treatment on growth rate. After 46 days, the 0·5 mg/kg treatment group had proportionately 0·35 more body fat (P < 0.01), higher body fat content (P < 0.01), higher total body energy (P < 0.05) and higher total body energy content (P < 0.05). Experiment 1 linked reduced growth rate with increased corticosterone concentrations and experiment 2 suggested the mechanism may be a repartitioning of energy storage to lipid. However, it was not determined whether these consequences were a direct effect of guanfacine or a secondary effect due to corticosterone. In spite of reductions in energy expenditure, guanfacine retards growth in rats and mice, but not in cattle where growth is enhanced. Thus rodents may have a limited usefulness as models for studies of α2-adrenoceptor agonists in cattle.

Type
Growth, development and meat science
Copyright
Copyright © British Society of Animal Science 2002

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baxter, J. D. and Rosseau, G. G. 1979. Glucocorticoid hormone action: an overview. In Glucocorticoid hormone action (ed. Baxter, J. D. and Rosseau, G. G.), pp. 124. Springer-Verlag, Berlin.Google Scholar
Birnbaum, S. G., Poddell, D. M. and Arnsten, A. F. T. 2000. Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats. Pharmacology, Biochemistry and Behaviour 67: 397403.Google Scholar
Folch, J., Lees, M. and Stanley, G. H. S. 1957. A simple method for the isolation and purification of total lipids from animal tissues. Journal of Biological Chemistry 226: 497509.CrossRefGoogle ScholarPubMed
Gazzola, C. 1993. α2-Adrenoceptor-mediated effects on resting energy expenditure. International Journal of Obesity 17: 637641.Google Scholar
Gazzola, C., Magner, T., Lisle, A. T. and Hunter, R. A. 1995. Effects of α-adrenoceptor agonists and antagonists on metabolic rate in cattle. Comparative Biochemistry and Physiology 111A: 73-77.CrossRefGoogle Scholar
Huang, H., Gazzola, C., Pegg, G. G. and Sillence, M. N. 1998. Effect of corticosterone on β-adrenoceptor density in rat skeletal muscle. Journal of Animal Science 76: 9991003.CrossRefGoogle ScholarPubMed
Hunter, R. A. 1992. The effect of the α2-adrenoceptor agonist, guanfacin, on the energy metabolism of steers fed low-quality roughage diets. British Journal of Nutrition 67: 337343.CrossRefGoogle Scholar
Hunter, R. A., Sillence, M. N., Gazzola, C. and Spiers, W. G. 1993. Increasing growth rates of cattle by reducing maintenance energy requirements. Australian Journal of Agricultural Research 44: 579595.CrossRefGoogle Scholar
Lafontan, M. and Berhan, M. 1981. Alpha-adrenergic receptors and the regulation of lipolysis in adipose tissue. Trends in Pharmacological Science 2: 126129.Google Scholar
Lawes Agricultural Trust. 1998. Genstat 5, release 1·3. Rothamsted Experimental Station, Harpenden, UK.Google Scholar
Macy, J. D., Beattie, T. A., Morgenstern, S.E. and Arnsten, A. F. T. 2000. Use of guanfacine to control self-injurious behaviour in two rhesus macaques (Macaca mulatta) and one baboon (Papio anubis). Comparative Medicine 50: 419425.Google Scholar
Munos-Hoyos, A., Fernandez-Garcia, J.M, Molina-Carballo, A., Macias, M., Escames, G., Ruiz-Cosano, C. and Acuna-Castroviejo, D. 2000. Effect of clonidine on plasma ACTH, cortisol and melatonin in children. Journal of Pineal Research 29: 4853.CrossRefGoogle Scholar
O’Neill, J., Halgren, E., Marinkovic, K., Siembieda, D., Refai, D., Fitten, L. J., Perryman, K. and Fisher, A. 2000. Effects of muscarinic and adrenergic agonism on auditory P300 in the macaque. Physiology and Behavior 70: 163170.CrossRefGoogle ScholarPubMed
Scholtysik, G. and Fetrovska, N. 1987. Pharmacology of guanfacine. Cor Vasa 29: (suppl. 1) S11S16.Google ScholarPubMed
Scholtysik, G., Jerie, P. and Picard, C. W. 1980. Guanfacine. In Pharmacology of antihypertensive drugs (ed. Scriabine, A.), pp. 7998. Raven Press, New York.Google Scholar
Sillence, M. N. and Etherton, T. D. 1991. Cortisone arrests growth but enhances the inductive effect of porcine growth hormone on plasma IGF-1 concentrations in female rats. Journal of Animal Science 69: 28152821.Google Scholar
Sillence, M. N., Matthews, M. L., Spiers, W. G. and Lindsay, D. B. 1990. Effects of an α2-agonist on growth and metabolic rate in mice. Proceedings of the Nutrition Society of Australia 15: 170.Google Scholar
Sillence, M. N., Matthews, M. L., Spiers, W. G., Pegg, G. G. and Lindsay, D. B. 1991. Effects of clenbuterol, ICI 1118551 and sotalol on the growth of cardiac and skeletal muscle and on β2-adrenoceptor density in female rats. Naunyn-Schmiedeberg’s Archives of Pharmacology 344: 449453.CrossRefGoogle Scholar
Spiers, W. G., Sillence, M. N. and Lindsay, D. B. 1990. α2-Agonist-induced effects on growth in rats. Proceedings of the Nutrition Society of Australia 15: 172.Google Scholar
Swartz, B. E., Kovalik, E., Thomas, K., Torgersen, D. and Mandelkern, M. A. 2000. The effects of an alpha-2 adrenergic agonist, guanfacine, on rCBF in human cortex in normal controls and subjects with focal epilepsy. Neuropsychopharmacology 23: 263275.Google Scholar
Thomas, K. M. and Rodway, R. G. 1983. Effect of trenbolone acetate on adrenal function and hepatic enzyme activities in female rats. Journal of Endocrinology 98: 121127.Google Scholar