Doutorado em Ciências Fisiológicas Multicêntrico (ICB)
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Item Alterações cardiometabólicas em ratos submetidos ao desmame precoce farmacológico induzido por bromocriptina(Universidade Federal de Goiás, 2021-10-25) Silva, Gabriel Camargo da; Gomes, Rodrigo Mello; http://lattes.cnpq.br/3121095341590269; Gomes, Rodrigo Mello; Pansani, Aline Priscila; Paes, Antonio Marcus de Andrade; Oliveira, Júlio Cezar de; Wutzow, Kesia Gemima Palma RigoExclusive breastfeeding during the first six months of life is fundamental important for the child's health. Nutritional and environmental disorders during the lactation period promote epigenetic changes that culminate in metabolic dysfunctions in the offspring throughout the life. Thereby, interrupting lactation before the established period can cause, among other changes, obesity and hypertension during adulthood. This work aimedto evaluate the cardiometabolic disruptions in Wistar rats that were submitted to pharmacological early weaning, induced by bromocriptine. After birth, sexing was carried out to form litters containing six males per mother and two groups were formed: early weaning (DP) and control (CT). In the last 3 days of lactation, mothers belonging to the DP group received daily injections (0.5 mg - twice daily) of bromocriptine. During the lactation period, the pups’ body weight was monitored on days 1, 7, 14, 18, 19, 20 and 21. After, the offspring were separated and kept in boxes containing three animals each. For 180 days, food intake and body weight were monitored weekly. After this period, was performed measurements of cardiovascular parameters. Subsequently, contractile function of the left ventricle and coronary reactivity were assessed during the ischemia/reperfusion protocol using the Langendorff technique and aortic vascular reactivity through the isolated vessel in an organ bath. Finally, the animals were euthanized and the organs were collected for histological analysis and Western blot. The animals in the DP group developed obesity phenotypeincrease in adipose tissue. Interestingly, there was no increase in food intake. During the recording of cardiovascular parameters in the awake animals, an increase in MAP, SP, DP and HR was observed in animals submitted to DP. Baseline coronary flow was reduced in animals in the DP group and, after reperfusion, it was significantly increased. In addition, it was verified the presence of cardiac remodeling in the animals of the DP group, from the presence of interstitial fibrosis andcardiomyocytes hypertrophy. Finally, we showed low protein expression of the AT1 and MAS receptors, antioxidant enzyme SOD and Akt protein expression. The present study demonstrated that pharmacological DP induced by maternal bromocriptine injections, caused obese phenotype and increase in blood pressure and heart rate. Thus, for the first time, it was demonstrated that pharmacological DP promoting cardiovascular changes, suggesting that this model triggers cardiometabolic programming, negatively affecting these animals during adulthood.Item Avaliação do uso de aditivos aliados ao manejo alimentar no desenvolvimento do trato digestivo de bezerros(Universidade Federal de Goiás, 2021-04-14) Caixeta, Luis Fernando de Sousa; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/0207928273284808; Ferreira, Reginaldo Nassar; http://lattes.cnpq.br/2555785079833283; Ferreira, Reginaldo Nassar; Biancardi, Manoel Francisco; Leão, Karen Martins; Mendes, Elizabeth Pereira; Moreira, Tainá SilvestreThis study examines the effect of restricted feeding, based on the amount of milk supplied, combined with the compensatory gain mechanism and supplementation with an essential amino acid (methionine analogue - MET) or essential oils (EO) on the intestinal development and intestinal health of calves. Twenty calves were weighed and subjected to four treatments (feeding regimes) for two 28-day periods, as follows: Treatment 1 (RES+MET) - restricted milk intake in the first period (3 L/animal/day) and no restriction in the second period (6 L/animal/day) plus 4 g MET/day in both periods; Treatment 2 (MET) - no milk restriction in either period (6 L/animal/day) plus 4 g MET/day in both periods; Treatment 3 (RES+EO - milk restriction in the first period (3 L/animal/day) and no restriction in the second period (6 L/animal/day) plus 1.5 g EO/day in both periods; and Treatment 4 (EO) - no milk restriction in either period (6 L/animal/day) plus 1.5 g EO/day in both periods. Weight change in period 1 was lower in the animals on RES+MET than in the MET group, and no difference was detected between the other groups. Total live weight change at the end of the experiment was similar between the groups. There were no differences between treatment groups and periods for serum lactate, alkaline phosphatase or creatinine levels. Total proteins differed between the periods in the RES+MET, RES+EO and EO groups. Rumen papillae height was lower in the restricted groups. The methionine analogue reduced morphological changes in the hepatocyte nucleus as a result of the nutritional mechanisms induced by compensatory gain. Intestinal integrity was maintained by the action of the methionine analogue. Essential oils enhance the expression of GHS-R1a receptors in the hypothalamus.Item Contribuição dos aferentes sinoaórticos nos ajustes renais, cardiovasculares, simpáticos e ventilatórios induzidos por hiperosmolalidade aguda(Universidade Federal de Goiás, 2017-01-20) Silva, Elaine Fernanda da; Colombari, Eduardo; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4721289A2; Pedrino, Gustavo Rodrigues; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4762065Z5; Braga, Valdir de Andrade; Silveira, Nusa de Almeida; Ferreira, Patrícia Maria; Castro, Carlos Henrique de; Colombari, EduardoThe forebrain is suggested the main sensorial site for monitoring changes in plasma osmolality. In addition to the central mechanisms, it has been suggested that peripheral sensors may participate in the osmoregulation. In the present study we investigated the contribution of the sinoaortic afferents in the physiological mechanisms of regulation of the body fluids tonicity during acute hyperosmolality. In the first part of the study, we explored the participation of sinoaortic afferents in the cardiovascular, renal and autonomic responses induced by hypernatremia. Wistar rats (280-350 g) were anesthetized with halothane (2% in O2) and submitted to sinoaortic denervation (SAD), carotid body removal (CBX) or fictitious surgery, and implantation of cannula in the right femoral artery and vein to blood pressure (BP) recording and substance administration, respectively. In the next day, SAD animals were anesthetized with urethane (1.2 g/kg body weight, i.v.) and instrumentalized for renal sympathetic nerve activity (rSNA) recording. Non-anaesthetized CBX animals were used to BP recording and renal excretion test. The parameters were evaluated in response to intravenous infusion of hypertonic saline (HS) (3 mol/L NaCl, 1.8 mL/kg body weight, in 60 seconds). Renal sympathoinhibition induced by infusion of HS was abolished in SAD rats (SAD: -10.7 ± 5.5% of baseline, vs. control rats: -28.7 ± 4.8% of baseline, 60 minutes after HS, p<0.05). CBX attenuated the pressor response (CBX: 5.7 ± 2.0 mmHg, vs. control: 15.8 ± 2.0 mmHg, 12 minutes after HS; p<0.05) and sodium renal excretion (CBX: 74.9 ± 7.3%, vs. control: 99.7 ± 6.7%, 90 minutes after HS; p<0.05) to HS. These results show that the integrity of the aortic and carotid afferents are essential for autonomic, cardiovascular and renal adjustments induced by acute hypernatremia. In the second part we explored the involvement of the carotid bodies and forebrain in the autonomic and ventilatory responses induced by intra arterial infusion of HS using arterially-perfused in situ rat preparations (male Holtzman rats, 60-100 g). HS infusions (0.17; 0.3; 0.7; 1.5 and 2 mol/L NaCl; 200 µL during 20 seconds each) were performed in accumulative ascending order while thoracic sympathetic, phrenic and carotid sinus nerve activities were recorded. Intra-arterial infusion of 2 mol/L NaCl, produced a modest increase in phrenic burst frequency (5.8 ± 0.9 bpm, vs. Ringer: 0.4 ± 0.2 bpm, p<0.05) and markedly enhanced sympathetic (63.3 ± 8.4%, vs. Ringer: -0.8 ± 1.9%, p<0.05) and carotid sinus nerve activities (105.1 ± 13.2%, vs. Ringer: -0.2 ± 1.3%, p<0.05). Carotid bodies removal attenuated the sympathoexcitation (26.2 ± 4.9%, p<0.05), but not the tachypnea (3.6 ± 0.5 bpm) induced by 2 mol/L NaCl. The forebrain disconnection at the pre-collicular level, abolished the sympathoexcitation (8.4 ± 3.7%, p<0.05) and the increase in phrenic burst frequency (1.2 ± 0.4 bpm, p<0.05) in response to 2 mol/L NaCl. The results indicate the participation of forebrain in the sympathetic and ventilatory responses produced by sodium overload. Moreover, they suggest that carotid bodies may act as a sodium peripheral sensor contributing for the autonomic responses to acute hyperosmotic challenges.Item Papel da grelina e do receptor GHS-R1a no controle da função renal e hemodinâmica em animais normotensos e hipertensos(Universidade Federal de Goiás, 2019-03-14) Silva, Elder Sales da; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/0207928273284808; Ferreira, Reginaldo Nassar; http://lattes.cnpq.br/2555785079833283; Custódio, Carlos Henrique Xavier; Ferreira, Patrícia Maria; Gomes, Rodrigo Mello; Gingozac, Marc Alexandre Duarte; Ferreira, Reginaldo NassarGhrelin (GRE) is a 28-amino acid peptide that depends on the acylation of serine at position 3 to act as a signaling molecule on growth hormone secretagogues (GHS-Rs). Its function depends on this interaction and these receptors are expressed in several tissues which may imply multisystemic actions. The objective of this research was to evaluate the responses related to renal and hemodynamic function in normotensive and hypertensive rats through administration of ghrelin and GHS-R1a agonists (MK0677) and antagonists (PF04628935). For this purpose, mice were used as experimental models being normotensive (WT) and spontaneously hypertensive (SHR). The following experimental designs were established: 1) Rats were injected subcutaneously (sc) vehicle (VEH) (NaCl 0,9%), ghrelin (GRE) (10μg / kg), GHS-R1a AT antagonist (PF04628935) (0.4mg / kg), ghrelin + PF0462893 or GHS-R1a agonist AGO (MK0677) (10μg / kg) and maintained in metabolic cages for further urinary and plasma analysis. 2- WT and SHR animals received intravenous (i.v.) injections of ghrelin (10 / kg), PF04628935 (0.4 mg / kg) or a combination of ghrelin and PF04628935 for vascular conductance record. 3 - GHS-R1a receptor expression was evaluated by Western blot in the aortic artery, renal artery, cortex and renal medulla. Metabolic parameters (renal function) revealed significant differences in relation to water and feed intake as well as urinary volumes in both the Wistar and SHR treated groups. The same was observed for free water and creatinine clearance in addition to osmolarity and urinary sodium and potassium levels. Intravenous injection of ghrelin reduced mean blood pressure in both strains without evoking significant chronotropic changes. Ghrelin increased Renal Vascular Conductivity (CVR) in SHR rats. The hypotensive and vasomotor effects (CVR) produced by ghrelin in SHR mice were reversed by the specific antagonism of GHS-R1a with PF04628935 (20 minutes after ghrelin injection), for all analyzes was determined (p <0.05). GHS-R1a receptor expression was shown to be decreased in the renal cortex of SHR animals. Thus, the data obtained suggest possible participation of ghrelin and GHR-S1a receptors in renal function and hemodynamic adjustments of normotensive and hypertensive rats.Item Manipulações alimentares em diferentes fases do desenvolvimento de bovinos(Universidade Federal de Goiás, 2019-02-22) Costa, Natália Alves; Nassar, Reginaldo Ferreira; http://lattes.cnpq.br/2555785079833283; Pansani, Aline Patrícia; Araujo Neto, Francisco Ribeiro de; Castanheira, Marlos; Santos, Fabiana Ramos dosThe objective of this study was to evaluate the physiological, biochemical and metabolic effects of milk restriction and prebiotic supplementation in suckling calves, and the same effects of supplementation of taurine in the bovine termination phase. Two experiments were executed to achieve the mentioned objectives. In the first trial it was used 20 crossbred calves with approximate initial weight of 38 kg and housed in individual pens for 56 days divided into two periods of 28 days each. The animals were allocaded in four experimental groups: animals receiving 6 L of milk in periods 1 and 2 (CON), animals with 50% milk restriction in the first period and re-alimented in the second period (RES), animals without restriction and supplemented of 5 g/day of mannanoligosaccharide (MOS) or mannan- frutoligosaccharide (MFOS). The weight gain and feed intake were verified. Serum was used to determinate glucose, lactate, creatinine, alkaline phosphatase, triglycerides, urea, toal protein and the hormones ghrelin and leptin. In the brain, in the paraventricular region of the hypothalamus, ghrelin receptor expression (GHS-R1a) was evaluated. The rumen and small intestine were used to evaluate the development of the gastrointestinal tract: rumen papilla length, villus height and intestinal crypt depth. We observed a lower weight gain of the restricted group in the first period and no difference in the weight gain among groups in the second period. It was observed that animals from the prebiotic supplemented (MOS) group showed a significant increase in jejunal villus height. Ruminal development was favored by the supplementation of mannanoligosaccharides (MOS group), which significantly increased ruminal papillae length. No difference was found for serum concentration of ghrelin and leptin among treatments in periods 1 and 2 (P> 0.05). Regarding the expression of ghrelin receptors in the paraventricular region of the hypothalamus, there was no difference between the groups evaluated. The second experiment was performed in 123 days with 80 finishing steers, mean initial weight of 507 kg and divided into groups supplemented with: 0; 0.025; 0.05; 0.075 and 0.1% taurine in the diet. Changes in performance were evaluated by weighing and control of the daily feed intake, carcass traits were evaluated after animals slaughter with data provided by the slaughter hose, and the metabolic changes were measured by plasma glucose, lactate, taurine and triglycerides values. Immediately after slaughter, a sample of Sternocephalicus ventrally muscle was collected to analyze the glycolytic potential. To complement the data from the second in vivo assay, an in vitro assay was performed using ruminal fluid cultures. Measurements included concentrations of VFA, pH, IVDMD and fermentative gas production for cultures containing 0; 0.025; 0.05; 0.075 and 0.1% taurine on the substrate. Supplementation of taurine did not affect the final characteristics of weight, HCW, DMI and carcass traits. Blood metabolites were not affected by administration of taurine. In addition, the production of in vitro gases, the concentrations of IVDMD and VFA’s were not affected by the addition of taurine. A linear response was detected for pH (P = 0.006) and with cattle consuming 0.1% taurine had the lowest pH. The compensatory gain presented by the restrictd milk animals, but did not accelerate the intestinal and ruminal development, while the supplementation of mananoligosaccharides caused an accelerated growth of the ruminal papillae and villi of the jejunum. Mannan-frutoligosaccharide supplementation did not accelerate the development of suckling calves. Taurine supplementation did not cause any change in the finishing phase of cattle, however, it caused a decrease in rumen pH.