Ractopamine hydrochloride (RAC) has been used in the pig production industry for over 30 years. RAC is a beta-adrenergic agonist which is supplemented in the feed during the last 28 days prior to harvesting in finisher pigs to modify the pig's metabolism such that nutrients are redirected to favour muscle accretion rather than adipose deposition, and hence improve growth efficiencies, feed utilisation and carcass revenues. The objective of this study was to investigate the effect of dietary ractopamine (Paylean®) supplementation at levels of 0, 5, and 10 mg.kg-1 (hereafter referred to as 0-RAC, 5-RAC, and 10-RAC respectively) on animal growth performance, efficiency and carcass characteristics including daily voluntary feed intake, feed efficiency, absolute daily growth rate (ADG) and daily live weight gain, and backfat thickness for the last 27 days in finishing gilts. In this 27-day study, a homogenous group of 71 grower gilts (LW = 43 ± 1 kg) were pre-selected at a source farm. The gilts were then housed in similar and equally sized group pens at the Hatfield experimental facility of the University of Pretoria and fed a standard maize-soya oilcake based grower ration formulated to contain 0.94% standardised ileal digestible Lys (1.05% total Lys) and 14.01 MJ ME kg-1 during the 28 day pre-adaptation phase. From these gilts, individuals were weighed and 58 gilts selected (average LW = 68.7 ± 4.3 kg), and placed into individual pens and the same diet for 7 days (adaptation phase), afterwhich they were assigned to 1 of 3 treatments in a completely randomized block design with 19, 19, and 20 replicate pens per treatment. The pigs were then fed a standard maize-soya oilcake finisher (treatment) diet containing either 0-RAC, 5-RAC or 10-RAC for 27 d before harvesting. All treatment diets were formulated to contain 1.02% standardised ileal digestible Lys (1.13% total Lys) and 13.96 MJ ME kg-1. Individual pig LW, P2 thickness and pen feed disappearance were recorded weekly to determine LW changes, ADG, ADFI, and G:F. After 27 d on trial, gilts were slaughtered and carcass measurements were recorded at 24 h post-mortem. Overall, RAC supplementation did not affect ADFI or P2 (P > 0.05) but did influence LW (P = 0.049) and overall G:F (P = 0.012) after d27. At d15-d21 and d22-27, only a tendency (P = 0.169, 0.104 respectively) for a linear decrease in G:F with RAC supplementation was found. RAC also affected HCY (P= 0.045) and CCY (P = 0.045) but not fat depth, meat depth or fat % (P > 0.05). These results indicate that RAC may have small but beneficial effects in modern pig production, but further research is required to optimize concentrations and duration of supplementation in modern lean pig genotypes. / Dissertation (MSc (Agric))--University of Pretoria, 2016. / Animal and Wildlife Sciences / MSc (Agric) / Unrestricted

The cardiovascular system helps maintain blood pressure and blood flow to the different organ systems through many elaborate mechanisms. These mechanisms include the different blood vessels, each with their own properties, as well as both neural and humoral factors. The vessels that are most relevant here are arterioles, also known as resistance vessels, as they play a significant role in regulating organ blood flow, vascular resistance, and blood pressure in many different physiological conditions, such as exercise. More specifically, the focus of this paper is the endothelial layer of the arteriolar wall and its role in attenuating sympathetic adrenergic vasoconstriction, or sympatholysis. Exercising skeletal muscle cells require an increase in blood flow to adequately meet their oxygen and nutrient demands. In order to accomplish this, there is an increase in cardiac output by the heart and also a redistribution of blood flow away from inactive regions towards active muscle cells. This critical redistribution of blood flow depends on the sympathetic nervous system, which increases in activity during contraction to cause vasoconstriction of the arterioles that supply other inactive organs except the brain. Despite this increase in sympathetic nerve activity, there is also profound vasodilation in the microvasculature of active skeletal muscle cells. It is this paradox that helps match the increase in metabolism with an increase in blood flow during exercise, and it is also this mechanism that has been coined ‘functional sympatholysis.’ Although much effort has been put into studying the mechanism through which functional sympatholysis occurs, the existing data and evidence are not sufficient to deduce a clear picture at this time. There are inconsistencies regarding the functional distribution of alpha-adrenergic receptors, the role of non-adrenergic receptors, the impact of many different metabolic factors, and finally also the contribution of non-metabolic factors. Due to such contrasting data, it is clear that further research will need to be conducted in order to obtain a concrete explanation for sympatholysis. A recent study has postulated that the process of sympatholysis may primarily involve the endothelium. This study used various manipulations that involved endothelium-dependent vasodilatory responses as well as endothelium-independent vasodilatory responses intersected with sympathetic adrenergic nerve activity to determine that only those vasodilatory agents that functioned using the endothelium were able to attenuate sympathetic adrenergic vasoconstriction. This compelling evidence has made way for further inquiry into the endothelium’s role in this very important process. Due to the fact that the greatest amount of research has been devoted to studying the contraction-related attenuated responsiveness of alpha-adrenergic receptors, a hypothetical study and its various methods are proposed in this paper. This hypothesis states that both adenosine triphosphate and flow-mediated dilation, two vasodilatory stimuli that rely on a functional endothelium, are sympatholytic agents, whereas adenosine, which acts on vascular smooth muscle to cause vasodilation, is not sympatholytic. The conclusions that might be drawn from such a study and their various implications are also discussed. Finally, the major relevancy in this topic relates to the fact that sympatholysis or impaired sympatholysis may be a factor in many metabolic and cardiovascular diseases along with exercise. Some of the diseases discussed here are type II diabetes, hypertension, and chronic myocardial infarction. A concrete understanding of the mechanism by which this process occurs would potentially help invent new treatment plans and prevention. At this point, it seems probable that the endothelium does play a significant role in sympatholysis, but whether it is the primary dictator and whether there are also other influences that are absolutely essential still remains relatively uncertain.

Phenylethanolamine-N-methyltransferase (Pnmt), is the enzyme that catalyzes the conversion of noradrenaline to adrenaline. It has been found in the embryonic heart and in certain adult heart cells, including intrinsic cardiac adrenergic cells, intracardiac neurons, and cardiomyocytes, but their physiological role in the heart is not well understood. To determine the function of Pnmt-expressing cells in the developing heart, a novel genetically-targeted mouse model that causes selective cellular suicide of Pnmt-expressing cells was created by mating Pnmt-Cre Recombinase knock-in mice (PnmtCre/Cre) with ROSA26-eGFP-DTA (R26R+/DTA). The “cellular suicide” allele is the Diptheria Toxin A (DTA) gene fragment. Activation of the DTA suicide allele is dependent upon Cre expression, which is under the control of the endogenous Pnmt gene locus (i.e., expression is restricted to adrenaline-producing “adrenergic” cells). Ongoing studies in Dr. Ebert’s laboratory have shown that Pnmt-Cre/DTA mice have a loss of adrenergic cells in the adrenal gland and begin developing serious cardiac and neurological deficits within one month after birth. The purpose of my project is to examine the potential cardiac consequences of selective adrenergic cell ablation in this model. Aim 1 of this study is to analyze echocardiography data from mice with genetic ablation of adrenergic cells compared to age-matched (littermate) controls over the first 6-months after birth. Preliminary evidence indicates that there is substantial loss of function that progressively worsens with age in the ablation group compared to controls. Aim 2 of this study seeks to uncover evidence of adrenergic cell ablation in the heart using histological and immunofluorescence staining techniques. We predict that these experiments will provide physiological and anatomical evidence showing that Pnmt-expressing cells in the heart make significant contributions to cardiac development and function. This knowledge is expected to increase our basic understanding about the specific roles adrenergic cells play during heart, and could lead to the development of novel treatment strategies for certain types of cardiac defects in the future.

No description available.

No description available.

The bovine polymorphonuclear leukocyte (neutrophil) is a central component of the acute inflammatory response, and is capable of reacting to a myriad of pro-inflammatory chemical signals that have been characterized in the context of bovine respiratory disease (BRD). Human neutrophils and bovine macrophages are known to react to pro-inflammatory signals as well; however, they are also capable of responding to anti-inflammatory signals from the autonomic nervous system. In particular, activation of the beta2-adrenergic receptor on these cells decreases several aspects of inflammatory activity, including reactive oxygen species production, chemotaxis, degranulation, and inflammatory mediator production. Dysfunction of beta-adrenergic receptors is known to contribute to the pathophysiology of numerous diseases in both people and animals. For example, congestive heart failure, asthma, cystic fibrosis, atopic dermatitis, pheochromocytoma, myasthenia gravis, hypertension, and sepsis have all been linked to decreased beta1- / beta2-adrenergic receptor density (depending on the cell type) and / or uncoupling of the respective receptor from its effector enzyme, adenylyl cyclase. Dysfunction of the beta2-adrenergic receptor mechanism has also been described in pulmonary airway and vascular smooth muscle tissue from cattle, sheep, and rats exposed to Manheimia haemolytica, which provides insight into the pathophysiology of BRD. Despite the prominent role of the bovine neutrophil in the acute inflammatory stage of BRD, and despite the potential for dysfunction following excessive exposure to inflammatory stimuli, there are no reports that describe the presence of the beta2-adrenergic receptor on bovine neutrophils, nor function of the components responsible for its signal transduction cascade. Without complimentary work with bovine neutrophils, using data from human neutrophils to examine treatment options for the acute inflammatory stage of BRD is unrealistic. For this reason, the present dissertation proposed that 1) bovine neutrophils possess the beta2-adrenergic receptor mechanism, 2) components of the beta2-adrenergic receptor mechanism work in concert to increase bovine neutrophil adenosine 3,5-cyclic monophosphate (cAMP) levels and suppress superoxide anion production, and 3) the beta2-adrenergic receptor mechanism is dysfunctional following exposure to inflammatory stimuli. Using the nonselective beta1- / beta2-adrenergic receptor antagonist [3H]CGP-12177 we observed a maximum specific binding density (Bmax) value of 0.19 fmol per 100,000 bovine neutrophils. Although this value is approximately equal to what we observed with dairy cow neutrophils, human neutrophil Bmax values with this radioligand are anywhere from five to ten-fold greater, which suggests a significant species difference. We further defined the adrenergic receptor population on bovine neutrophils to be dominated by the beta2-subtype. Next, we characterized the function of beta2-adrenergic receptors by stimulating cAMP production with the beta2-adrenergic receptor agonist, terbutaline. The role of the beta2-subtype was confirmed when the terbutaline-mediated effect was negated by ICI-118,551, a beta2-adrenergic receptor antagonist. Also, the role of the phosphodiesterase enzyme in cAMP recycling in bovine neutrophils was illustrated, as the terbutaline-mediated rise in cAMP concentration was dependent upon phosphodiesterase inhibition by 3-isobutyl-1-methylxanthine (IBMX). This study confirms the anti-inflammatory nature of the beta2-adrenergic receptor on bovine neutrophils by demonstrating the ability of terbutaline and IBMX to decrease superoxide anion production in a dose-dependent manner. The synthetic cAMP analog, 8-bromo-cAMP also decreased superoxide anion production, but the effect was time-dependent because of its need to diffuse across the cell membrane. Moreover, IBMX exaggerated the terbutaline-mediated effect on superoxide anion production, while cAMP exaggerated the IBMX-mediated effect on superoxide anion, demonstrating that the beta2-adrenergic receptor acts in concert with adenylyl cyclase, while the phosphodiesterase enzyme functions to decrease their signal. By increasing the dose of the inflammatory stimulant opsonized zymosan eight-fold, we were able to eliminate the ability of various concentrations of terbutaline and IBMX to reduce superoxide anion production. We sought to provide a more specific demonstration of this phenomenon by activating protein kinase C (PKC) via phorbol 12-myristate 13-acetate (PMA) administration. However, preincubation with PMA actually increased terbutaline-mediated cAMP production, in a dose and time-dependent manner. At this time, we cannot explain why increasing the dose of opsonized zymosan and PMA had opposite effects on beta2-adrenergic receptor mechanism function. The answer may reside in the many reported functions of PKC isoforms. Additional studies that identify the PKC isoform repertoire in bovine neutrophils may illustrate the potential for selective inhibition, and may lead to more specific identification and treatment of beta2-adrenergic receptor mechanism dysfunction. Also, it remains to be seen how the various components of the bovine neutrophil beta2-adrenergic receptor mechanism function in-vivo during the acute inflammatory stage of BRD. / Ph. D.

Músculos esqueléticos de ratos idosos apresentam uma reduzida capacidade de se regenerar após lesão. No presente estudo, nós lançamos a hipótese de que a estimulação farmacológica de adrenoceptores b2 em músculos de ratos idosos lesados poderia melhorar a regeneração destes. Ratos jovens e idosos foram tratados com injeção subcutânea do agonista b2-adrenérgico formoterol (2 mg/kg/dia) durante 10 e 21 dias após lesão do músculo sóleo. Os músculos de ratos idosos lesados e tratados com formoterol por 10 e 21 dias apresentaram menor processo inflamatório e fibras musculares em regeneração com maior calibre quando comparados aos músculos apenas lesados. O tratamento com formoterol preveniu a queda da força tetânica e aumentou a síntese de proteínas e a fosforilação de mTOR em músculos de ratos idosos lesados e avaliados após 10 dias. Nossos resultados sugerem que o formoterol melhora a capacidade regenerativa estrutural e funcional dos músculos esqueléticos de ratos idosos, e que esse efeito é mediado pelo aumento da síntese protéica através da ativação de mTOR. / Skeletal muscles from old rats fail to completely regenerate following injury. In the present work, we hypothesized that pharmacological stimulation of b2-adrenoceptors in aged muscles following injury could improve their regenerative capacity. Young and aged rats were treated with a subcutaneous injection of b2-adrenergic agonist formoterol (2 mg/kg/day) up to 10 and 21 days after soleus muscle injury. Formoterol-treated muscles from old rats evaluated at 10 and 21 days post-injury showed reduced inflammation and regenerating myofibers of greater caliber when compared to their injured controls. Formoterol minimized the decrease in tetanic force and increased protein synthesis and mTOR phosphorylation in old muscles at 10 days post-injury. Our results suggest that formoterol improves structural and functional regenerative capacity of regenerating skeletal muscles from aged rats by increasing protein synthesis via mTOR activation.

Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains xii, 263 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 233-242).

Neonatal ventral hippocampus (nVH) lesioned animals show molecular and behavioral abnormalities analogous to those described in schizophrenia. As an extension to previous studies that showed an increase in ligand binding of cortical alpha-1 adrenergic receptors (AR) and a dysfunction in alpha-1 AR regulation of mesolimbic dopamine functions in post-pubertal nVH lesioned rats, we investigated the subcellular expression and activity of protein kinase C (PKC)---a second messenger in alpha-1 AR signaling---in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) of post-pubertal nVH lesioned rats. Western blot analysis of membrane and cytosolic fractions showed complex changes in lesioned animals in the expression of different PKC subtypes following saline or alpha-1 AR agonist (cirazoline i.p.) injection. Among these changes, nVH lesioned animals showed a significant increase in membrane bound PKC alpha and phospho-PKC, and a decrease in cytosolic PKC gamma and PKC betaII in the PFC in comparison to sham-lesioned controls following saline. Cirazoline increased membrane bound PKC alpha in controls but decreased it in lesioned animals. In the NAcc, lesioned animals showed an increase in membrane bound and cytosolic PKC epsilon and PKC lambda levels following saline. Following cirazoline, lesioned animals showed a decrease in membrane bound PKC epsilon and PKC lambda, while controls showed an increase in cytosolic and membrane fractions of PKC epsilon with no change in PKC lambda. In vitro PKC activity assays showed increased basal activity in PFC slices of lesioned animals compared to controls, with no difference in NAcc slices. alpha-1 AR stimulation by the agonist phenylephrine (PE) increased PKC activity in PFC of controls while decreasing activity substantially in lesioned animals. In the NAcc, high concentrations of PE increased activity in controls, but decreased activity in lesioned animals. This abnormal expression and activity of PKC in the PFC and NAcc of nVH lesioned animals may be related to abnormal alpha-1 AR functions and may modulate some of the abnormal neuronal functions in these animals, such as working memory deficits and hyper neuronal excitability of the PFC and the NAcc.

Thesis (doctoral)--University of Lund, 1995. / Added t.p. with thesis statement inserted.