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Atrial wall stretch plays an important role in regulating the secretion of ANF, a cardiac peptide hormone that regulates water and salt balance, as well as blood pressure. Yet the precise cellular mechanism that couples mechanical stretch to ANF secretion is unknown. In order to elucidate this mechanism, we investigated the role of heterotrimeric Gi/o proteins in mechanically-stimulated ANF secretion. G proteins act as molecular switches that have been implicated in the control of intracellular protein transport, and stretch-secretion coupling. We utilized a pharmalogical agent, pertussis toxin (PTX), to inhibit Gi/o proteins in male Sprague Dawley rats. The effect of stimulating Gi/o proteins was also investigated using Mastoparan-7 (MAS-7; 10-5 M). Infusion with MAS-7 for 30 minutes potently stimulated ANF secretion; a response attenuated by. Results suggest that Gi/o proteins couple atrial muscle stretch to ANF secretion in an acute setting, and that there exist two mechanisms, which control natriuretic peptide secretion. The first mechanism controls stretch-stimulated ANF secretion and is PTX-sensitive, while the second regulates basal ANF release and is PTX-insensitive. (Abstract shortened by UMI.)

Experiments were performed in vivo using an extra-corporeal blood loop (EC-loop), on chronically cannulated adult rainbow trout ( Oncorhynchus mykiss) to determine whether the ability of fish to respond to acute hypoxia was impaired by an intravenous nicotine infusion (1.3 x 10-5 mol kg-1 h -1; designed to desensitise chromaffin nicotinic receptors). Respiratory and cardiovascular measurements taken throughout the nicotine infusion of the desensitisation protocol indicate that non-chromaffin, neuronal nicotinic receptors also appear to be stimulated and to desensitise. The next set of experiments showed that despite nicotinic receptor desensitisation induced by intravenous infusion of nicotine, plasma catecholamine levels were increased to similar levels (adrenaline plus noradrenaline = 125--200 nmol l-1) as in control fish during severe hypoxia (40--45 mm Hg). (Abstract shortened by UMI.)

High-resolution crystal structures of the human ABO blood group glycosyltransferase enzymes, unliganded and in complex with substrate molecules, reveal the basis for their substrate specificity and suggest amino acid residues important in catalysis. The human ABO(H) blood group glycosyltransferases differ in only 4 amino acid residues and are therefore two of the most homologous, naturally occurring glycosyltransferases known that utilize different naturally occurring donor molecules. An N-acetylgalactosaminyltransferase (GTA) uses a UDP-GalNAc donor to convert the H-antigen to the A-antigen, while a galactosyltransferase (GTB) uses a UDP-Gal donor to convert the H-antigen to B antigen. The resulting A and B blood group antigens differ from each other only in the substitution on the terminal saccharide residue of an acetamido for an hydroxyl group yet the potentially catastrophic effects of a mismatched blood transfusion makes them a paradigm for specificity in biosynthetic and immune recognition. The crystal structures of the catalytic domains of the cloned blood-group A and B enzymes have been determined to 1.80 and 1.65 A resolution, respectively, and those of the catalytic domains of the A and B enzymes in complex with the H antigen disaccharide and UDP to 1.35 and 1.32 A resolution, respectively. Glycosyltransferases that retain the stereochemistry of the donor sugar, such as GTA and GTB, have been postulated to function via a double-inversion mechanism, including a nucleophilic attack on the donor sugar anomeric carbon. The current structures support the double inversion mechanism and reveal, remarkably, that only two of the amino acids differing between GTA and GTB are positioned to select between the two donors and thus contribute to the stringent stereo- and regioselectivity in this biosynthesis. In addition, the structures of GTA and GTB in complex with H antigen alone have been determined to 1.58 and 1.46 A resolution, respectively, and show that, contrary to expectations, the acceptor substrate can bind in the absence of the donor substrate. The DxD motif in GTA and GTB coordinates a manganese ion, which in turn interacts with the UDP-sugar donor. Comparison of the GTA and GTB structures to the other two retaining glycosyltransferases (bovine alpha1-3galactosyltransferase, N. meningitidis LgtC) structures determined to date reveals that the coordination between the aspartate residues and manganese ion are the same. Interestingly, this coordination pattern is different from those observed in inverting glycosyltransferases, suggesting that these patterns may be characteristic of inverting versus retaining glycosyltranserases. The structure of an antibody fragment specific for the human blood group A trisaccharide antigen has also been determined to near-atomic resolution. This structure shows a pronounced pocket at the antigen-binding site, which is formed by four of the six complementarity determining regions, and is of the appropriate size and shape to accommodate the terminal N-acetylgalactosamine residue of the A trisaccharide antigen. A model of the Fv-trisaccharide complex shows several protein-carbohydrate interactions that would allow specific recognition of the blood group A antigen acetamido group.

The role of carbohydrate metabolism is not yet established in fish. Therefore, the goal of my thesis was to quantify the rate of hepatic glucose production (Ra glucose) during aerobic exercise in fish. During sustainable exercise, mammals strongly stimulate their rate of hepatic glucose production to replace the additional glucose consumed by locomotory muscles and this increase in Ra glucose may be regulated by circulating catecholamines. By analogy with mammals, I hypothesized that sub-maximal exercise in trout will increase hepatic glucose production above resting levels. Circulating catecholamines were also measured to establish their possible influence in stimulating Ra glucose. To test this hypothesis, I measured the rate of appearance of glucose in rainbow trout swimming for 3 h at 1.5 body lengths s-1. Results indicated that circulating EPI could be a possible candidate for regulating Ra glucose during exercise. Therefore, I investigated the effects of sympathetic EPI on Ra glucose (1) by infusing exogenous EPI to increase plasma concentrations and (2) by blocking the effect of sympathetic EPI via beta-adrenoreceptors with propranolol (PROP). I hypothesized that EPI will stimulate whereas PROP will depress hepatic glucose production. (Abstract shortened by UMI.)

Previous studies showed that beta2-adrenergic agonists (beta 2-AAs) enhanced muscle growth and reduced lipid deposition in animals of agricultural and economical importance, including teleost fish. The goal of the present study was to provide a mechanistic explanation underlying the reported beta2-AA-induced muscle growth in the rainbow trout (Oncorhynchus mykiss). Using radioligand binding assays and adenylyl cyclase/cAMP assays, this study characterized and demonstrated the presence of functional beta2-adrenoceptors (beta2-ARs) on red and white muscle membranes. Trout fed 40 ppm of two beta2-AAs (clenbuterol and ractopamine) for 30 days showed no significant changes in measured body and physiological parameters, beta2-AR numbers or beta2-AR mRNA levels in red or white muscle. However, treatments significantly increased fractional protein synthesis rates in red and white muscle. These studies demonstrate that beta2-AAs impact muscle protein synthesis by mechanisms initiated at the muscle membrane beta 2-AR and include the beta2-AR-signalling pathway in a teleost fish.

The purpose of this study was to determine the functional role of six prominent leg muscles during knee extension. Changes in muscle-tendon length and EMG activity were looked at in conjunction with the results from an inverse dynamics analysis. The muscles investigated were the monoarticular vastus lateralis, soleus, gluteus maximus and the biarticular biceps femoris, rectus femoris and gastrocnemius. Four female and five male elite rowers performed on a Gjessing rowing ergometer while kinematic information was recorded on cinefilm. The force applied to the stretcher, the force applied to the oar handle and the EMG activity were sampled simultaneously. Through inverse dynamics, net moments of force at the ankle, knee and hip joints and powers from these moments were computed for one drive. The results showed a difference in the use of knee extensors by female and male rowers. For the females, the power produced originated exclusively from the hip extensors. This contrasts with the results obtained from the male subjects where power was produced by hip and knee extensors. Plausible explanations include differences in anatomical structures between both sexes (skeletal dimensions, tendon attachments location, muscle mass distribution), differences in rowing technique and deficiency in the knee extensor strength. Paradoxical activity appeared to take place in the recruitment of the biarticular gastrocnemius and biceps femoris during the extension of the knee. More intriguing was the detection of paradoxical activity from the action of m. rectus femoris at the hip which it seemed to extend.

In order to study the effects of mild hypercapnia on sleep and thermoregulation, 5 male volunteers (23.6 +/- 1.96 yrs) were exposed to air containing 0, 2, or 4% CO2, while sleeping in a double (9.0 clo) or single (4.5 clo) Canadian Forces sleeping ensemble (1 clo = 0.155°C·m 2·W-1) at -20°C. Each condition was presented twice in a completely randomized manner on non-consecutive nights. Standard polysomnographic EEG, EMG and EOG measures were monitored as well as rectal (Tr), mean skin (T¯sk) and toe (T toe) temperatures. Hypercapnia was associated with enhanced body cooling as indicated by a decreased time to minimal Tr and Ttoe (p < .05). In agreement with current knowledge of sleep in cold environments, sleeping in the single bag resulted in a significantly decreased percentage of REM sleep (p < .05) and trends towards decreases sleep efficiency and total sleep time (TST). Slow wave sleep (%SWS) tended to increase in the single bag condition. CO2 exposure was associated with a trend towards decreased TST and suppression of the cold induced increase in %SWS. The possible effects of body temperatures being mediated through sleep processes as opposed to direct CO2 effects, and the possible importance of SWS on thermoregulation were discussed.

Par cette recherche, nous voulons verifier si en ajoutant une mesure de ratio taille/hanches et une mesure du niveau de pratique d'activite physique aux activites regulieres de depistage de facteurs de risque de maladie cardiovasculaire, nous pourrons ameliorer notre capacite d'identifier les individus qui ont un risque accru de developper cette maladie. La litterature demontre les liens qui existent entre l'obesite abdominale determinee par le ratio taille/hanches, le niveau de pratique d'activite physique et les taux de HDL et de LDL. On reconnait egalement, qu'un taux de HDL inferieur a 0,9mmol/L et/ou qu'un taux de LDL superieur a 3,4 mmol/L jumeles a un taux de cholesterol total superieur ou egal a 5,2mmol/L constitue un risque accru de developper une maladie cardiovasculaire. Soixante-et-un (61) sujets masculins ages entre 35 et 64 ans ont participe a cette recherche. On a recueilli aupres de ceux-ci, de donnees de ratio taille/hanches, d'habitudes de vie, de pratique d'activite physique ainsi que des mesures de poids, taille et pression arterielle et des mesures sanguines de cholesterol total, de HDL, de LDL et de triglycerides. Les analyses de variance et le test de Tukey ne nous demontrent pas l'existence de differences significatives, des taux de HDL et LDL, entre les groupes d'hommes hypercholesterolemiques sedentaires et actifs et entre les hommes hypercholesterolemiques ayant un ratio taille/hanches eleve et bas.

The purposes of this study were to (1) compare the pressor response between isometric exercise and a cold pressor test (CPT) and (2) examine the pressor response to isometric exercise at 33% of maximal voluntary contraction (MVC) combined with a CPT applied either at the onset or during the last minute of a 2-min CPT. Ten normotensive male volunteers performed isometric handgrip (HG) at 33% MVC, cold foot immersion, HG combined with a simultaneous CPT, and HG performed during the last minute of a 2-min CPT in a random order over three days. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were recorded at rest and continuously throughout the tests. The results of this study indicate that (1) the pattern of HR response between the 2-min HG and the CPT was different; (2) DBP values during CPT for the initial 30s and the last 15s were significantly lower than DBP corresponding values during HG, while there were no significant differences between the CPT and HG with respect to SBP response; (3) when HG and CPT were performed simultaneously, the effects on SBP and HR were additive, whereas the effects on DBP and MAP were not; (4) CPT performed for 1 minute prior to HG attenuated the SBP and HR responses to HG at 33% MVC, and (5) although both HR and BP increased in response to HG at 33% MVC, only BP increased progressively in a linear fashion when combined with CPT. (Abstract shortened by UMI.)