Growth and adipose tissue metabolism in young pigs fed cimaterol with adequate or low dietary protein

The beta-adrenergic agonist, cimaterol, was fed to young growing pigs to determine whether the carcass compositional changes observed in finishing pigs fed a beta-adrenergic agonist would be manifest in young animals. Furthermore, because cimaterol increased the deposition of lean mass in finishing pigs, it could have a protein sparing effect in young pigs that are rapidly accreting muscle mass and have a high dietary protein requirement. Pigs were fed cimaterol (at 0, .25 and .50 mg X kg-1 diet) and either an adequate (18%) or restricted (14%) protein diet from about 10 to 60 kg body weight. Pigs that were fed the 14 compared with 18% protein diet grew slower and ate less but had the same gain-to-feed ratio. These pigs also had shorter carcasses, less lean muscle and more fat deposition (assessed by carcass measurements and carcass chemical composition) than pigs that received adequate protein. Plasma protein and albumin concentrations were greater and plasma cholesterol, triglyceride and fatty acid concentrations were lower in pigs fed high compared with low dietary protein. Dietary cimaterol had no effect on any of the growth or carcass variables or on adipose tissue metabolism. When fed the high protein diet, cimaterol-supplemented pigs had smaller livers and stomachs. Dietary cimaterol did not have any major detectable effects on these young pigs, nor was there any evidence for a protein sparing effect.     

Effect of beta-adrenergic agonists on lipolysis and lipogenesis by porcine adipose tissue in vitro

The effects of the beta-adrenergic agonists isoproterenol, cimaterol, ractopamine and clenbuterol on lipolysis (release of glycerol and free fatty acids) and lipogenesis (incorporation of 14C into fatty acids from [14C]glucose) was examined in porcine adipose tissue explants in vitro. Lipolysis was stimulated by isoproterenol, cimaterol or ractopamine but not by clenbuterol. Insulin reduced the lipolytic effects of the beta-adrenergic agonists (isoproterenol, cimaterol and ractopamine). Lipogenesis was inhibited by all beta-adrenergic agonists tested (isoproterenol, cimaterol, ractopamine and clenbuterol). The antilipogenic effect of the beta-adrenergic agonists was reduced by the presence of insulin in the incubation. Although effects of the different beta-adrenergic agonists varied, all had some direct effects that could be expected to reduce adipose accretion. Effects of beta-adrenergic agonists in the pig are due in part to direct effects on adipose tissue.     

Effects of cimaterol on muscle protein metabolism and its actions in hypothyroid and hyperthyroid rats.

Objectives were to examine mechanisms underlying anabolic actions of cimaterol in skeletal muscle and to evaluate cimaterol's actions in hypothyroid and hyperthyroid rats. In the first study growing rats were fed either a control diet or a diet containing cimaterol for 10 days. In a second study sham-thyroidectomized and thyroidectomized (Tx) rats were assigned to one of 5 treatments: control (sham-Tx), Tx, Tx supplemented with cimaterol, Tx injected with triiodothyronine (T3), and Tx rats injected with T3 and supplemented with cimaterol. Effects of treatments on growth, muscle weights and urinary NT-methylhistidine (NMH) excretion were evaluated in both trials. Muscle was also collected for determinations of DNA, RNA, protein and activities of several proteolytic enzymes. Cimaterol caused muscle hypertrophy and increased urinary NMH excretion. Hence, anabolic actions of cimaterol may result from an increase in myofibrillar protein synthesis which exceeds changes in myofibrillar protein degradation. Urinary NMH excretion was reduced by thyroidectomy and increased in hyperthyroid rats and both hypothyroidism and hyperthyroidism were characterized by myopathy. Cimaterol increased muscle weights in hypothyroid but not in hyperthyroid rats. Therefore, cimaterol's anabolic properties are thyroid hormone-independent and antagonized by excess thyroid hormone. Anabolic actions of cimaterol in hypothyroid rat muscle were attributed to an action on protein synthesis because urinary NMH excretion was not affected by cimaterol but muscle RNA concentration was increased. Activities of cathepsins B, D and L and neutral proteinase were dose-related to thyroid status, however, were unrelated to cimaterol-dependent perturbations in NMH excretion. Control of muscle protein balance by thyroid hormones may involve regulation of these enzymes; however, control of muscle protein degradation by cimaterol is likely directed towards other proteolytic mechanisms or to mechanisms which alter susceptibility of myofibrillar proteins to degradation.     

Combined effects of clenbuterol and various concentrations of protein on performance of broiler chickens

1. The effects of the beta-adrenergic agonist, clenbuterol (1 mg/kg diet) on the growth and muscle composition in female broiler chickens (14 to 32 d of age) fed on diets containing various concentrations of protein (220, 240 or 260 g protein/kg) were examined. 2. Body weight gain over the 18 d period increased linearly with increasing protein intake. The rate of gain was significantly higher in clenbuterol-treated chickens than in control birds. 3. Dietary clenbuterol increased thigh muscle weight and protein concentration of breast and thigh muscle, regardless of dietary protein content. Protein/DNA ratio in thigh muscle was enhanced by clenbuterol feeding, and the magnitude of difference of the ratio was higher in chickens fed on the 240 and 260 g CP/kg diets than in those fed the 220 g CP/kg diet. 4. It was concluded that clenbuterol-treated chickens require increased dietary protein to maintain maximal growth, and that increased protein consumption is an important factor in improving growth in clenbuterolfed broilers.     

Regulation of uterine estrogen receptors (ER) by beta-adrenergic stimulation in immature rats

The effects of a 3-day intramuscular (i.m.) administration of clenbuterol (25 μ.g/ Kg), propranolol (12 mg/kg), clenbuterol (25 μg/kg) plus propranolol (12 mg/ Kg) and estradiol (0.5 μg) upon the female reproductive system were investigated in immature Sprague-Dawley rats. Clenbuterol and estradiol treatments induced a significant increase in uterus weight and in relative uterus weight, whereas in the groups treated with propranolol and clenbuterol plus propranolol no differences were detected versus controls. The uterine estrogen receptor levels were significantly increased by clenbuterol administration. In the rats dosed with propranolol and clenbuterol plus propranolol, no modifications occurred in estrogen receptor concentrations when compared with control values. Uterine progesterone receptors were never significantly affected by any of the considered treatments. Data obtained indicate that clenbuterol treatment induces an increase in uterus weight and in estrogen receptor levels and that these effects are regulated by acute beta-adrenergic stimulation, as the contemporaneous administration of high doses of a beta-blocker inhibit such effects.     

Evaluation of cimaterol for finishing swine including a drug withdrawal period

One hundred fifty crossbred pigs (55 kg) were allotted by weight, sex and litter to a randomized complete-block design with five dietary treatments, six blocks per treatment and five pigs per pen with sex equalized across treatments. Corn-soybean meal-based diets (.65% lysine) with 0, .25 and .5 mg/kg cimaterol were fed, on an ad libitum basis, to pigs slaughtered at an average pen weight of 104 kg/pig. Drug withdrawal prior to slaughter was 1, 3 and 5 d for pigs fed cimaterol at .25 mg/kg and 1 d for those fed cimaterol at .5 mg/kg of diet. Dietary cimaterol level influenced (quadratic, P less than .01) average daily gain during the first 42 d on test; however, daily feed intake and feed conversion ratio were not affected (P greater than .1). Pigs fed .25 mg/kg cimaterol with a 1-d drug withdrawal had 6.8, 7.7 and 13.5% less 10th rib fat depth and 11.1, 6.1 and 13.3% less P2 fat depth than those subjected to either a 3- or 5-d drug withdrawal or those fed the 0 mg/kg cimaterol diet (control), respectively. Overall, pigs fed cimaterol had 7.9% larger longissimus muscle area and 2.6% more kilograms of muscle than pigs fed the control diet. Cimaterol fed at .5 mg/kg resulted in higher (P less than .05) Warner-Bratzler shear force values and altered the proportion of saturation in some long-chain fatty acids, although the total saturated:unsaturated fat ratio was not affected. Pigs fed no cimaterol had less thaw loss (P less than .05) than did those fed other treatments.(ABSTRACT TRUNCATED AT 250 WORDS)     

beta-Adrenergic receptor agonists increase apoptosis of adipose tissue in mice

beta-Adrenergic receptor (beta-AR) agonists increase muscle mass and decrease body fat in rodents and livestock. With oral administration, however, the effects of beta1-AR and beta2-AR can be different, depending on the species tested. We tested the effects of clenbuterol, a beta2-AR agonist, and ractopamine, a beta1/beta2-AR agonist, on growth, adiposity and adipose tissue apoptosis in male and female mice by feeding diets containing control, 200 ppm clenbuterol, or 200 or 800 ppm ractopamine. Food intake (FI) was measured daily; body weight (BW) and temperatures (BT) were measured on days 0, 3, 7, 10, 14, 17, and 20. On day 21 mice were sacrificed, body composition was determined using PIXImus densitometry, and muscle and adipose tissues were collected. There were no treatment effects on BT, FI, BW, feed efficiency or body composition. Retroperitoneal (Rp) and epididymal/parametrial (Epi/Par) fat pad masses were reduced in both 800 ppm ractopamine (40+/-3mg and 207+/-20mg, respectively) and clenbuterol (35+/-7 mg and 211+/-22 mg) treated mice compared to control (66+/-8 mg and 319+/-30 mg, P<0.05). Brown adipose tissue (BAT) mass was greater (P<0.05) in clenbuterol treated mice compared to other treatments. Adipose tissue apoptosis (% DNA fragmentation) was increased in Epi/Par fat pads in clenbuterol (5.2+/-1.1%) and 800 ppm ractopamine (4.1+/-0.8%) treated mice compared to control (1.7+/-0.4%, P<0.05). These findings show that WAT apoptosis can be induced by activation of beta-AR in mice, although the mechanism is unknown.     

Cimaterol-induced muscle hypertrophy and altered endocrine status in lambs

The objectives of this study were 1) to determine how cellular growth of skeletal muscle is altered by the repartitioning agent cimaterol and 2) to determine if cimaterol alters endocrine status in association with its repartitioning effects. Thirty Dorset wether lambs were randomly assigned to a pre-treatment baseline group or received 0 or 10 ppm cimaterol in a complete, mixed, high-concentrate diet for 7 or 12 wk. Weights of biceps femoris (BF), semimembranosus (SM) and semitendinosus (ST) muscles were 32.8, 27.1 and 31.5% greater, respectively, in treated lambs at 7 wk, and were 22 to 24% greater at 12 wk. Longissimus (LD) cross-sectional area was 26 and 32% greater at these treatment intervals. Percent type I fibers declined significantly over the course of the experiment in ST, SM and LD, and cimaterol caused a small but significant reduction in percent type I fibers in the ST at 7 and 12 wk. Muscles from lambs fed cimaterol contained 50 and 75% more fibers that exhibited negative staining for phosphorylase activity. Mean cross-sectional area of type I and type II fibers in the combined portions of the ST were 30.4 and 29.3% greater, respectively, in cimaterol-fed lambs after 12 wk, while type I and type II fiber areas in the longissimus were only 13 and 15% greater, respectively. Cimaterol-induced hypertrophy of the ST resulted in both protein and RNA content being 30 to 35% greater (P less than .01) at 7 and 12 wk, while DNA concentration was 22% less (P less than .01) at 7 wk. DNA concentration returned to normal by 12 wk. These results indicate that cimaterol elicits a rapid increase in muscle RNA and protein accretion without concurrent incorporation of satellite cell nuclei. Plasma insulin and insulin-like growth factor-1 (IGF-1) concentrations were 55 and 34% lower, respectively, in cimaterol-fed lambs. Plasma somatotropin concentration and area under the curve were 2.3 times greater (P less than .01) in lambs fed cimaterol for 6 wk, while plasma cortisol, prolactin and glucose concentration were unaffected at 6 or 12 wk. The significant changes in endocrine status may be important in the mechanism(s) of cimaterol in altering muscle accretion.     

Clenbuterol and the horse revisited

Clenbuterol is a beta(2)-agonist and potent selective bronchodilator that is used to treat bronchospasm in the horse. The drug is normally administered to horses orally as a syrup formulation. Once absorbed into the systemic circulation, clenbuterol has the potential to cause many side effects, including a repartitioning effect and major alterations in cardiac and skeletal muscle function. Recent studies have also reported that clenbuterol can affect bone and the immune, endocrine and reproductive systems. A great deal of information has been published on the beneficial effects of short term therapeutic doses of clenbuterol on the equine respiratory system, although there is limited information about chronic administration, particularly since this has been associated with adverse physiological effects on other systems. This review summarizes the relevant understanding of clenbuterol for clinicians and horse owners who may administer this drug to pleasure and performance horses.     

超高效液相色谱-串联质谱法检测氟苯尼考固体制剂中9种β-受体激动剂

采用0.1 mol/L盐酸-甲醇（1∶1）提取,0.1%甲酸溶液稀释,BEHC18色谱柱分离,串联质谱分析,对氟苯尼考固体制剂中克伦特罗、莱克多巴胺、沙丁胺醇、西马特罗、西布特罗、妥布特罗、马布特罗、特布他林、氯丙那林等9种β-受体激动剂非法添加物进行检测分析。9种β-受体激动剂在系列浓度范围内呈现良好线性关系,相关系数r2均大于0.990;9种药物在氟苯尼考固体制剂中的检出限为500 mg/kg,定量限为1000 mg/kg,回收率为90.8%--103.4%,批内、批间相对标准偏差均小于10%。结果表明,该方法简便快捷、定性准确,适用于该类药物在氟苯尼考固体制剂中的检测。     

Differential effects of dexamethasone and clenbuterol on rat growth and on beta2-adrenoceptors in lung and skeletal muscle

Beta-adrenergic agonists increase growth rate, but their efficacy is reduced over time as the number of beta2-adrenoceptors in muscle decreases. Dexamethasone increases beta2-adrenoceptor density in many tissues, but this effect has not been reported in skeletal muscle. In this study, male rats were treated daily for 10 d with either clenbuterol (4 mg/kg of feed), dexamethasone (.2 mg/kg BW, s.c.), or clenbuterol plus dexamethasone. Untreated rats served as controls. Dexamethasone caused a marked suppression of growth rate, which resulted in decreased (P < .001) body weight (-29%), carcass weight (-30%), hind-limb muscles (-22%), omental fat (-22%), and heart weight (-10%). Feed intake was reduced (-26%), but feed conversion efficiency was also impaired (P < .001). Clenbuterol caused a small increase in growth rate (+6%; P < .05), with an increase in leg muscle (+7%; P < .01) and heart mass (+8%; P < .05). Feed efficiency was improved (P < .001) by clenbuterol. Rats given the combined treatment still showed a reduction in growth rate (-81%). Clenbuterol caused only a mild attenuation of the effects of dexamethasone on feed intake, BW, and carcass weight, but reduced the catabolic effect of dexamethasone on hind-limb muscle to only -8%. Clenbuterol caused a slight increase in the affinity beta2-adrenoceptors in lung for binding to the radioligand (-)[125I]iodocyanopindolol. Relative to control values, the density of beta2-adrenoceptors in lung was +31% with dexamethasone treatment, -45% with clenbuterol, and -23% with the combined treatment. Clenbuterol also decreased beta2-adrenoceptors in skeletal muscle (-35%), but so did dexamethasone (-13%), so the effects of the beta-adrenergic agonist were not attenuated through use of the combined treatment (-40%). The results show that the inductive effect of glucocorticoids on beta2-adrenoceptors is tissue-specific and that glucocorticoid treatment is not a useful adjunct to beta-adrenergic agonist treatment in animal production.     

超高效液相色谱-串联质谱法检测动物肌肉组织中19种β-受体激动剂残留

建立了猪、牛和羊肌肉组织中吡布特罗、西马特罗、特步他林、齐帕特罗、沙丁胺醇、西布特罗、克伦塞罗、克伦丙罗、羟甲基克伦特罗、氯丙那林、莱克多巴胺、克伦特罗、妥布特罗、福莫特罗、溴布特罗、克伦潘特、班布特罗、马布特罗和马喷特罗等19种β-受体激动剂残留检测的超高效液相色谱-串联质谱方法.猪、牛和羊肌肉组织样品用乙腈和异丙醇（8：2,V/V）提取,加入NaC1、Na2SO4和MgSO4盐析去杂质.待测药物经BEH C18色谱柱分离,以0.1％甲酸乙腈溶液和0.1％甲酸水溶液为流动相进行梯度洗脱.同位素内标法和基质匹配标准溶液外标法定量.19种β-受体激动剂在系列浓度范围内呈现良好线性关系,相关系数r2均大于0.99;19种药物在肌肉组织中的检测限为0.25 μg/kg,定量限为0.5μg/kg.从0.5、1和5μg/kg三个添加浓度检测结果可以看出,19种药物的回收率为73.7％ ～ 114.1％,批内批间相对标准偏差均小于20％.结果表明,该方法简便快捷、灵敏度高、定性准确,适用于该类药物残留的检测.     

A comparison between clenbuterol, salbutamol and terbutaline in relation to receptor binding and in vitro relaxation of equine tracheal muscle

Beta₂-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine.
  We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, pre- contracted with 40 n m carbachol, in tissue chambers. The affinities of these drugs to the β₂-adrenoceptors in homogenates of the same muscle tissue were also examined. These experiments were performed with radioligand binding studies using the very potent β-adrenoceptor antagonist ¹²⁵I-cyanopindolol.
  The three drugs were almost equipotent in relaxing the muscle strips. The EC₅₀-values for salbutamol, terbutaline and clenbuterol were 5.6, 13.8 and 2.1 n m , respectively, and all three drugs relaxed the preparations completely. In the competitive binding study, however, the K_d-value of clenbuterol was much lower (24 n m ) than that of salbutamol and terbutaline (1100 n m and 3900 n m , respectively). The amount of receptors bound at the EC₅₀-value of clenbuterol was 8% compared to less than 1% for salbutamol and terbutaline. This indicates a lower intrinsic efficacy of clenbuterol than of the other two drugs. The β-adrenoceptor density was 45 ± 14.3 fmol/mg protein (mean ± SD) and the K_d-value of ¹²⁵I-cyanopindolol was 11.4 ± 3.3 p m .     

Effects of cimaterol on rabbit growth and myofibrillar protein degradation and on calcium-dependent proteinase and calpastatin activities in skeletal muscle

The objectives of this study were to examine effects of a beta-adrenergic agonist (cimaterol) on growth and muscle development in rabbits and to examine cimaterol's effects on myofibrillar protein degradation (MPD) and on activities of several proteolytic enzymes including the calcium-dependent proteinases (CDP). Twelve New Zealand White rabbits were assigned to either control diets or to diets containing cimaterol for 35 d, after which they were killed and effects on performance and tissue weight gains were determined. Urine was collected from d 21 through 28 from each rabbit for assessment of N tau-methylhistidine (NMH) excretion. Cimaterol increased rates of gain, efficiency of gain and skeletal muscle weights. Enhancement in muscle weight was associated with an increase in total DNA and with a reduction in NMH. Cimaterol did not affect activities of cathepsin B, cathepsin D or neutral serine proteinase, but it reduced activities of the millimolar and micromolar forms of the CDP by 58 and 57%, respectively, and it reduced activity of the inhibitor of the CDP (calpastatin) by 52%. Cimaterol-dependent myofibrillar protein accretion was likely mediated, at least in part, by a reduction in MPD. The change in MPD was associated with a reduction in muscle CDP activities. Cimaterol-dependent muscle hypertrophy therefore may involve changes in calcium-dependent proteolysis of myofibrillar proteins. The significance of the effects of cimaterol on calpastatin activity is not known.     

Single injection of clenbuterol into newly hatched chicks decreases abdominal fat pad weight in growing broiler chickens

The aim of the current study was to examine the effects of clenbuterol injection into newly hatched chicks on both the abdominal fat pad tissue weight and the skeletal muscle weight during subsequent growth. Twenty‐seven 1‐day‐old chicks were divided into two groups, receiving either a single intraperitoneal (i.p.) injection of clenbuterol (0.1 mg/kg body weight) or phosphate‐buffered saline (PBS). Body weight gain, feed intake and feed conversion ratio were not affected by clenbuterol injection during the 5‐week experimental period, while the abdominal fat pad tissue weight of the clenbuterol‐injected chicks was lower than that of the control chicks at 5 weeks post‐injection. Plasma non‐esterified fatty acid concentrations were significantly increased in the clenbuterol‐injected chicks, while plasma triacylglycerol concentrations did not differ. Additionally, the enzymatic activity of fatty acid synthase was lower in the liver of the clenbuterol‐injected chicks. Conversely, the skeletal muscle weights were not affected by clenbuterol injection. These results suggest that a single clenbuterol injection into 1‐day‐old chicks decreases the abdominal fat pad tissue weight, but may not affect skeletal muscle weights during growth. © 2015 Japanese Society of Animal Science     

Muscle protein turnover and tenderness in broiler chickens fed cimaterol

To investigate the impact of cimaterol (CIM) on muscle protein turnover, carcass and muscle composition, muscle cathepsin B + L activity and meat tenderness, 21-d-old broiler chickens (n = 88) were assigned to dietary treatments of either 0 or 1 ppm CIM. Fractional synthesis rates (FSR), fractional accretion rates (FAR), proximate composition and collagen content were determined in the breast muscle (BM); pectoralis major) and a group of leg muscles (LM; gastrocnemius and peroneous longus) from groups of six birds per treatment within each of two time periods (age = 38 or 56 d). Whole body composition, serum hydroxyproline content and BM cathepsin B + L activity also were measured. Fractional degradation rates (FDR) were calculated as the difference between FSR and FAR. Feeding CIM increased (P less than .01) whole body protein content. Weights of LM and percentage of body weight as BM and LM were increased (P less than .05) when CIM was included in the diet. Although FSR was not significantly reduced by CIM feeding it decreased (P less than .05) with increasing age. Due to decreases in FAR, FDR thereby was reduced by CIM 31.5% and 11.9% in BM and 38.2% and 37.4% in LM at 38 d and 56 d of age, respectively. Cathepsin B + L activities also were reduced 33.6% (P less than .01) and shear forces were increased by 41% (P less than .05) by CIM feeding. For chickens fed CIM, the correlation between cathepsin B + L activity and shear force was -.63 (P less than .01). Feeding CIM improved carcass leanness and muscling due to reductions in FDR and proteolytic enzyme activity. Feeding CIM also reduced meat tenderness.     

Cimaterol reduces beta-adrenergic receptor density in rat skeletal muscles.

Interactions between the beta-adrenoceptor agonist cimaterol and beta-adrenoceptors on rat skeletal muscle membranes were examined in two studies. In Exp. 1, muscle samples from eight Sprague-Dawley rats (female, approximately 200 g) were used for competition binding and autoradiographic studies using [125I]cyanopindolol (ICYP) as a radioligand. The affinities or dissociation constants for binding (KD values) for cimaterol in plantaris and soleus muscles were .68 and .92 microM, respectively. Muscle areas stained for succinic dehydrogenase had propranolol-resistant ICYP binding sites; cimaterol did not seem to compete for these sites. In Exp. 2, 60 Sprague-Dawley rats (female, approximately 218 g) were fed 0 or 10 ppm of cimaterol in rat diet that was ground. Groups were killed after 1, 3, 7, 14, or 28 d of treatment. Cimaterol increased BW gain up to 14 d after commencement of treatment, with little or no improvement thereafter. Enhanced weight gain in skeletal muscles also occurred up to 14 d of cimaterol treatment. Densities of beta-adrenoceptors in plantaris and soleus muscle membrane homogenates were estimated using a radioligand binding assay with ICYP. A significant reduction in the number of binding sites (Bmax) was observed after 3 d of cimaterol treatment in plantaris muscle without a change in the KD of ICYP binding. The percentage reductions in Bmax were 26.8, 42.2, 37.7, and 37.8% at 3, 7, 14, and 28 d after cimaterol administration, respectively. In the soleus muscle, significant reductions (44.1 and 29.8%) in Bmax were observed after 3 and 14 d of cimaterol treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute and Subacute Metabolic and Endocrine Effects of Clenbuterol in Female Pigs

The aim of the study was to assess the relationship between acute and subacute metabolic and endocrine effects after intravenous administration of the ₂-adrenergic agonist clenbuterol in a growth-promoting dose to female pigs. Acute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and nonesterified fatty acid (NEFA) concentrations during 300 min after a single administration of clenbuterol. Significantly higher serum insulin and NEFA concentrations (19.90±2.50 U/ml, p<0.01, and 0.69±0.04 mmol/L, p<0.001, respectively) were measured 30 min after the preprandial administration of clenbuterol in female pigs. Over the same period, the levels of blood glucose (4.42±0.30 mmol/L) showed no difference from those of control pigs. The postprandial serum NEFA concentration decreased moderately during 210 min after feeding. Postprandial blood glucose and insulin concentrations increased and reached maximal levels 120 min after clenbuterol administration (10.91±0.60 mmol/L and 85.22±7.24 U/ml, respectively), and returned to basal levels at 300 min (4.20±0.21 mmol/L and 7.75±1.60 U/ml, respectively) after the administration of clenbuterol. Subacute metabolic and endocrine effects were assessed by measuring the blood glucose, serum insulin and NEFA concentrations for 21 days after the repeated doses of clenbuterol. In addition, the influence of clenbuterol administration on the endocrine regulation of the onset of the next expected oestrus in female pigs was assessed by measuring their serum 17-oestradiol and progesterone concentrations. Blood glucose, serum insulin and NEFA concentrations after the last administration of clenbuterol did not differ significantly from those in control animals. The onset of the next expected oestrus occurred regularly without any significant difference in serum 17-oestradiol or progesterone concentrations between the treated (9.83±2.60 pg/ml and 0.15±0.03 ng/ml) and control pigs (8.52±2.70 pg/ml and 0.25±0.06 ng/ml). The study results suggest the duration of intravenous administration of clenbuterol in a growth-promoting dose necessary to influence the metabolic and endocrine activities in female pigs.     

Clenbuterol administration does not attenuate the exercise-induced pulmonary arterial, capillary or venous hypertension in strenuously exercising Thoroughbred horses

The present study was carried out to ascertain whether beta2-adrenergic receptor stimulation with clenbuterol would attenuate the pulmonary arterial, capillary and venous hypertension in horses performing high-intensity exercise and, in turn, modify the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Experiments were carried out on 6 healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications) and the clenbuterol (0.8 pg/kg bwt, i.v.) treatments. The sequence of these treatments was randomised for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, right heart/pulmonary vascular pressures were determined at rest, sub-maximal exercise and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate and induced EIPH in all horses. In the control experiments, incremental exercise resulted in progressive significant increments in right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures and all horses experienced EIPH. Clenbuterol administration to standing horses caused tachycardia, but significant changes in mean right atrial or pulmonary vascular pressures were not observed. During exercise performed after clenbuterol administration, heart rate as well as right atrial and pulmonary arterial, capillary and wedge pressures also increased progressively with increasing work intensity. However, these values were not found to be statistically significantly different from corresponding data in the control study and the incidence of EIPH remained unaffected. Since clenbuterol administration also does not affect the transpulmonary pressure during exercise, it is unlikely that the transmural force exerted onto the blood-gas barrier of exercising horses is altered following i.v. clenbuterol administration at the recommended dosage.