for lambs (Hanrahan et al., 1987) and pigs (Yen et al., 1990a,b; 1991). However, significant differences in responses among genotypes were observed in some comparisons (Warris et al., 1990; Gu et al., 1991a,b; Bark et al., 1992). Cimaterol and ractopamine increased skeletal muscle growth in both obese and lean genotypes of swine (Yen et al., 1990a,b; 1991), but anabolic responses to ractopamine were greater in genotypes that exhibited superior growth performance and carcass muscle and protein accretion rates than the inferior genotype to which they were compared (Bark et al., 1992; Gu et al., 1991b). Ractopamine-treated pigs of the inferior genotype still exhibited 12 kg less skeletal muscle mass than control pigs from the superior genotype when comparisons were made at similar body weights (Bark et al., 1992), which indicates that genotypic differences are not eliminated by β-agonist administration.

Responses to β-agonists in poultry tend to be, on a percentage basis, less significant than those seen in the mammals (see Table 2-5). This difference is probably caused by fundamental differences between adipose tissue metabolism and the type of β-receptor found in the muscle. There is, however, some evidence for the response in chickens to be related to the sex of the animal. Treatment of Hubbard × Hubbard broilers with cimaterol reduced carcass fat on the order of 10 percent in the female birds but only approximately 5 percent in the males (Dalrymple and Ingle, 1987). This sexual dimorphic effect may be caused by the tendency of female broilers to deposit more fat than their male counterparts. Cimaterol fed at 1 mg/kg to broiler chickens increased leg muscle weight more than breast muscle weight, and effects were greater after 56 days of treatment than after 38 days (Morgan et al., 1989). Cimaterol has also been shown to improve growth performance and body composition of ducks in a dose-dependent manner (W. F. Dean, Duck Research Laboratory, Eastport, Long Island, N.Y., personal communication, 1987). Ractopamine causes a dose-dependent improvement in growth performance, dressing percentage, and muscle content of turkeys when administered at the end of the feeding period (12 to 20 weeks) (Wellenreiter and Tonkinson, 1990a,b).

Although it is convenient to discuss en masse the β-agonists that seem to induce enhancement of skeletal muscle deposition and reduce carcass fat content, it should be remembered that marked differences are present in their structures, pharmacokinetics, and metabolism. Therefore, some differences in their mode of action and efficacy are to be expected.

The pharmacokinetic properties of β-adrenergic agonists will influence rates of absorption into the circulation, magnitude and temporal pattern of elevated concentrations in blood or plasma, and even selectivity for specific β-receptors (Timmerman, 1987). Variation among the compounds in how they are metabolized and eliminated from the circulation gives rise to estimated biological half-lives in rats ranging from 2 hours for fenoterol (Rominger and Pollmann, 1972) to 24 hours for clenbuterol (Kopitar and Zimmer, 1976). Species and mode of administration also contribute to variation among half-life estimates of the β-agonists. Published estimates of half-lives of β-agonists in farm animals are scarce. Affinity chromatography and high-performance liquid chromatography were used to describe the biphasic decline of plasma cimaterol concentration following a bolus intravenous injection in steers and yielded half-life estimates of 2.5 minutes for the distribution phase and 54 minutes for the elimination phase (Byrem et al., 1993). Biphasic elimination of clenbuterol in urine was demonstrated in veal calves fed 5 µg/kg BW twice daily for 3 weeks (Meyer and Rinke, 1991). Estimated half-life was 10 hours for the rapid phase and 2.5 days for the second phase. Half-life of clenbuterol in plasma could only be calculated for the fast phase and was estimated to be 18 hours. These estimates as well as those for other synthetic β-agonists developed for therapeutic use are much larger than for epinephrine and indicate that transfer to the peripheral compartment is very rapid. They also provide evidence that direct metabolic effects of cimaterol on specific tissues may be studied by close arterial infusion of cimaterol into specific vascular beds.

No formal proof exists for a common or shared set of specific actions of these compounds on skeletal muscle growth or lipid metabolism among all species in which they have been evaluated. The similar changes observed in protein and lipid deposition in growing animals suggest involvement of common effects. However, differences exist among the results of studies on mode of action. Review of the literature indicates that both quantitative and qualitative differences exist in the lipid metabolism response of different species to the same compound and of the same species to different compounds (Mersmann, 1989b). Similarly, attempts to block responses in muscle and adipose with receptor-specific compounds have given mixed results (Reeds et al., 1988; Choo et al., 1989). Therefore, caution must be exercised when drawing generalizations about mode of action of these compounds.

Treatment with β-agonists causes muscle hypertrophy rather than hyperplasia (Maltin et al., 1986; Beermann et al., 1987; Kim et al., 1987), but the response is not equal or not seen in all muscles (Beermann et al., 1986a; Bohorov et al., 1987; Dawson et al., 1988; Morgan et al., 1989). Responses in muscles containing a predominance of one fiber type (e.g., rat soleus) have been both greater than (Maltin et al., 1986) and equal to (Reeds et al., 1986; Thiel et al., 1987) responses

Front Matter (R1-R12)

Executive Summary (1-2)

1. Introduction (3-4)

2. Mechanisms of Action of Metabolic Modifiers (5-22)

3. Effect of Somatotropin on Nutrient Requirements of Dairy Cattle (23-29)

4. Effect of Metabolic Modifiers on Nutrient Requirements of Growing Ruminants (30-37)

5. Effect of Metabolic Modifiers on Nutrient Requirements of Growing Swine (38-51)

6. Effect of Metabolic Modifiers on Nutrient Requirements of Poultry (52-58)

References (59-73)

Authors (74-74)

Index (75-82)