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

Abstract

AbstractIn 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.