RESUMO
BACKGROUND: The precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL® ) tools were designed by industry to assist consumers with selecting safe foods for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason. OBJECTIVE: To assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process. METHODS: A web-based questionnaire was distributed to Australasian food and grocery manufacturers. RESULTS: One hundred and thirty-seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19-28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30-38), (n=204/600) of products that had undergone another (non-VITAL® ) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55-91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31-72) reported that it was too time-consuming and 36% (CI 95% 18-57) identified a concern with it not being endorsed by the government. CONCLUSION AND CLINICAL RELEVANCE: Currently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.
Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/imunologia , Indústria Alimentícia , Alimentos/efeitos adversos , Indústria Manufatureira , Percepção , Australásia/epidemiologia , Humanos , Internet , Prevalência , Medição de Risco , Inquéritos e QuestionáriosRESUMO
Australian underutilised fish species may serve as a potential source of valuable proteins and potent bioactive peptides. This novel research is the first to investigate the effects of storage-processing conditions and an in-vitro simulated gastrointestinal digestion (pepsin-pancreatin) on bioactive peptides' release during storage of fish fillet, derived from Australian silver warehou (Seriolella punctata). In-vitro bioactivities including angiotensin-converting enzyme and trypsin inhibitory and antioxidant activities were analysed. The antioxidant power was evaluated by DPPH free radical scavenging activity, Cu2+ chelating and Fe3+ reducing abilities. Fillets were stored at chilled (4 and 6 °C) and freezing (-18 °C) temperatures for 7 and 28 days, respectively. Results indicated that during postmortem storage, endogenous enzymes released from fillets an array of polypeptides during storage. The demonstrated physiological activities were further increased during simulated digestion. Bioactivities were greater at 4 °C, increasing over 7 days as compared to at 6 and -18 °C. An increase by 2 °C for chilled temperature was enough to cause significant changes in activities. The crude extracts obtained by pancreatin treatment demonstrated the highest metal chelating activities at 4 °C (86.3 ± 0.1 % on day 7). Physiological potency, especially metal chelating activity, of fillets obtained from silver warehou may be manipulated by storage conditions that would consequently be further enhanced during simulated digestion.
RESUMO
BACKGROUND AND PURPOSE: In diabetic nephropathy agonism of CB2 receptors reduces albuminuria and podocyte loss; however, the role of CB2 receptors in obesity-related nephropathy is unknown. The aim of this study was to determine the role of CB2 receptors in a model of diet-induced obesity (DIO) and characterize the hallmark signs of renal damage in response to agonism (AM1241) and antagonism (AM630) of CB2 receptors. EXPERIMENTAL APPROACH: Male Sprague Dawley rats were fed a high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks. In another cohort, after 9 weeks on a HFD, rats were injected daily with either 3 mg·kg(-1) AM1241, 0.3 mg·kg(-1) AM630 or saline for 6 weeks. KEY RESULTS: Ten weeks on a HFD significantly reduced renal expression of CB2 receptors and renal function. Treatment with AM1241 or AM630 did not reduce weight gain or food consumption in DIO. Despite this, AM1241 significantly reduced systolic BP, peri-renal adipose accumulation, plasma leptin, urinary protein, urinary albumin, urinary sodium excretion and the fibrotic markers TGF-ß1, collagen IV and VEGF in kidney lysate. Treatment with AM630 of DIO rats significantly reduced creatinine clearance and increased glomerular area and kidney weight (gross and standardized for body weight). Diastolic BP, glucose tolerance, insulin sensitivity, plasma creatinine, plasma TGF-ß1 and kidney expression of fibronectin and α-smooth muscle actin were not altered by either AM1241 or AM630 in DIO. CONCLUSIONS: This study demonstrates that while agonism of CB2 receptors with AM1241 treatment for 6 weeks does not reduce weight gain in obese rats, it leads to improvements in obesity-related renal dysfunction. LINKED ARTICLES: This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.
Assuntos
Rim/efeitos dos fármacos , Obesidade/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Animais , Canabinoides/farmacologia , Citocinas/metabolismo , Gorduras na Dieta/administração & dosagem , Fibrose , Indóis/farmacologia , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Masculino , Obesidade/patologia , Obesidade/fisiopatologia , Ratos Sprague-Dawley , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/antagonistas & inibidores , Aumento de Peso/efeitos dos fármacosRESUMO
Bioactive peptides are food derived components, usually consisting of 3-20 amino acids, which are inactive when incorporated within their parent protein. Once liberated by enzymatic or chemical hydrolysis, during food processing and gastrointestinal transit, they can potentially provide an array of health benefits to the human body. Owing to an unprecedented increase in the worldwide incidence of obesity and hypertension, medical researchers are focusing on the hypotensive and anti-obesity properties of nutritionally derived bioactive peptides. The role of the renin-angiotensin system has long been established in the aetiology of metabolic diseases and hypertension. Targeting the renin-angiotensin system by inhibiting the activity of angiotensin-converting enzyme (ACE) and preventing the formation of angiotensin II can be a potential therapeutic approach to the treatment of hypertension and obesity. Fish-derived proteins and peptides can potentially be excellent sources of bioactive components, mainly as a source of ACE inhibitors. However, increased use of marine sources, poses an unsustainable burden on particular fish stocks, so, the underutilized fish species and by-products can be exploited for this purpose. This paper provides an overview of the techniques involved in the production, isolation, purification, and characterization of bioactive peptides from marine sources, as well as the evaluation of the ACE inhibitory (ACE-I) activity and bioavailability.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Organismos Aquáticos/química , Descoberta de Drogas , Fragmentos de Peptídeos/uso terapêutico , Animais , Fármacos Antiobesidade/economia , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/metabolismo , Anti-Hipertensivos/economia , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/metabolismo , Proteínas Alimentares/química , Proteínas Alimentares/isolamento & purificação , Proteínas Alimentares/metabolismo , Proteínas Alimentares/uso terapêutico , Suplementos Nutricionais/economia , Descoberta de Drogas/tendências , Proteínas de Peixes/química , Proteínas de Peixes/isolamento & purificação , Proteínas de Peixes/metabolismo , Proteínas de Peixes/uso terapêutico , Indústria de Processamento de Alimentos/economia , Humanos , Hipertensão/dietoterapia , Hipertensão/tratamento farmacológico , Resíduos Industriais/análise , Resíduos Industriais/economia , Obesidade/dietoterapia , Obesidade/tratamento farmacológico , Oligopeptídeos/economia , Oligopeptídeos/isolamento & purificação , Oligopeptídeos/metabolismo , Oligopeptídeos/uso terapêutico , Fragmentos de Peptídeos/economia , Fragmentos de Peptídeos/isolamento & purificação , Fragmentos de Peptídeos/metabolismo , ProteóliseRESUMO
The consumption of a high fat diet (HFD) is associated with proteinuria and altered sodium handling and excretion, which can lead to kidney disease. In the proximal tubule, the Na(+) /H(+) Exchanger 3 (NHE3) is responsible for normal protein reabsorption and the reabsorption of approximately 70% of the renal sodium load. It is the Na(+) /K(+) -ATPase that provides the driving force for the reabsorption of sodium and its exit across the basolateral membrane. This study investigates the effects that consumption of a HFD for 12 weeks has on NHE3 and Na(+) /K(+) -ATPase expression in the kidney. Western blot analysis identified a significant reduction in NHE3 and its modulator, phosphorylated protein kinase B, in renal lysate from obese rats. In the obese rats, a reduction in NHE3 expression in the proximal tubule may impact on the acidification of endosomes which are responsible for albumin uptake, suggesting a key role for the exchanger in protein endocytosis in obesity. Western blot analysis identified a reduction in Na(+) /K(+) -ATPase which could also potentially impact on albumin uptake and sodium reabsorption. This study demonstrates that consumption of a HFD for 12 weeks reduces renal NHE3 and Na(+) /K(+) -ATPase expression, an effect that may contribute to the albuminuria associated with obesity. Furthermore the reduction in these transporters is not likely to contribute to the reduced sodium excretion in obesity. These data highlight a potential link between NHE3 and Na(+) /K(+) -ATPase in the pathophysiological changes in renal protein handling observed in obesity.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Regulação Enzimológica da Expressão Gênica , Rim/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Masculino , Obesidade/complicações , Obesidade/genética , Fosfoproteínas/metabolismo , Proteinúria/complicações , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/genética , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
Evidence from in vitro and in vivo studies has demonstrated the deleterious pathological effects of a dysregulated endocannabinoid system. Increased stimulation of the cannabinoid receptor 1 (CB1 ) and subsequent downstream cellular signalling are both causative in the deleterious pathological effects observed in a number of diseases. When the CB1 cell signalling cascade is blocked, this results in whole body weight-loss, leading to a reduction in obesity and associated co-morbidities. In the central nervous system; however, CB1 antagonism results in adverse psychological side effects. Blockade of CB1 via peripheral acting compounds that do not cross the blood-brain barrier have been determined to have beneficial effects in metabolic tissues such as the liver and skeletal muscle. These results support the notion that peripheral blockade of CB1 using pharmacological antagonists is a viable target for the treatment of the current epidemic of obesity and its associated co-morbidities.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Barreira Hematoencefálica/metabolismo , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Receptor CB1 de Canabinoide/antagonistas & inibidores , Redução de Peso/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Comportamento Alimentar , Feminino , Humanos , Masculino , Obesidade/tratamento farmacológico , Transdução de SinaisRESUMO
Gene knockout and agonist studies indicate that activation of the G protein-coupled receptor, GPR119, protects against diet-induced obesity and insulin resistance. It is not known if GPR119 activation in skeletal muscle mediates these effects. To address this uncertainty, we measured GPR119 expression in skeletal muscle and determined the effects of PSN632408, a GPR119 agonist, on the expression of genes and proteins required for fatty acid and glucose oxidation in cultured myotubes. GPR119 expression was readily detected in rat skeletal muscle and mRNAs were induced by 12 weeks of high-fat feeding. Treatment of cultured mouse C2C12 myotubes with 5 µM PSN632408 or 0.5 mM palmitate reduced expression of mRNAs encoding fatty acid oxidation genes to similar extents. More so, treatment with PSN632408 decreased AMPKα (Thr172 phosphorylation) activity in the absence of palmitate and ACC (Ser79 phosphorylation) activity in the presence of palmitate. In human primary myotubes PSN632408 decreased expression of PDK4 and AMPKα2 mRNA in myotubes derived from obese donors. These data suggest GPR119 activation in skeletal muscle may impair fatty acid and glucose oxidation.
Assuntos
Ácidos Graxos não Esterificados/metabolismo , Regulação da Expressão Gênica , Fibras Musculares Esqueléticas/metabolismo , Obesidade Mórbida/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ácidos Heterocíclicos/farmacologia , Adulto , Animais , Índice de Massa Corporal , Células Cultivadas , Células Clonais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Marcadores Genéticos , Glucose/metabolismo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Obesidade Mórbida/genética , Obesidade Mórbida/patologia , Oxidiazóis/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genéticaRESUMO
We examined the effect of ω-3 polyunsaturated fatty acid (PUFA) deficiency during development on sodium appetite. Being raised on an ω-3 PUFA deficient diet increased the intake of 0.5M NaCl following furosemide-induced sodium depletion by 40%. This occurred regardless of the diet they were maintained on later in life, and the increased consumption persisted for 3 days. In a second study, animals were administered furosemide and low-dose captopril. Sodium consumption of deficient raised animals was again higher than that of the control raised. Fos immunoreactivity in brain areas associated with sodium appetite and excretion were not influenced by diet. Our findings indicate that inadequate dietary ω-3 PUFA during development results in an exaggerated sodium appetite later in life.
Assuntos
Apetite , Deficiências Nutricionais/complicações , Ácidos Graxos Ômega-3/administração & dosagem , Cloreto de Sódio na Dieta/administração & dosagem , Sódio/deficiência , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Captopril/farmacologia , Feminino , Furosemida , Ratos , Ratos Sprague-DawleyRESUMO
Dehydrated mammals conserve body water by reducing thermoregulatory evaporative cooling responses e.g., panting and sweating. Increased core temperature (Tc) may result. Following rehydration and correction of fluid deficits, panting and sweating commence. We investigated the role of oropharyngeal/esophageal, postabsorptive and thermal signals in the panting response, and reduced Tc that occurs when unshorn sheep drink water following water deprivation for 2 days (ambient temperature 20 degrees C). Ingestion of water (at body temperature) resulted in increased respiratory rate (panting) and reduced Tc within 4 min that persisted for at least 90 min. Initially, a similar panting response and reduced Tc occurred following rehydration by drinking isotonic saline solution, but panting was not sustained after 20 min, and Tc began to rise again. Rehydration by intraruminal administration of water, without any drinking, resulted in delayed panting and fall in Tc. Intraruminal infusion of saline was ineffective. Rehydration by drinking cool water (20 degrees C) resulted in a rapid fall in Tc without increased panting. Shorn sheep had lower basal Tc that did not increase during 2 days of water deprivation, and they did not pant on rehydration by drinking water. Our results indicate that signals from the oropharyngeal and/or esophageal region associated with the act of drinking play a crucial role in the initial 20-30 min of the panting response to rehydration. Postabsorptive factors most likely reduced plasma tonicity and cause continued panting and further reduction in Tc. Tc also influences rehydration-induced panting. It occurs only if sheep incur a heat load during bodily dehydration.
Assuntos
Regulação da Temperatura Corporal , Desidratação/terapia , Ingestão de Líquidos , Esôfago/fisiopatologia , Hidratação , Orofaringe/fisiopatologia , Mecânica Respiratória , Resposta de Saciedade , Animais , Desidratação/sangue , Desidratação/fisiopatologia , Modelos Animais de Doenças , Feminino , Cabelo , Homeostase , Intubação Gastrointestinal , Soluções Isotônicas/administração & dosagem , Concentração Osmolar , Ovinos , Cloreto de Sódio/administração & dosagem , Fatores de Tempo , Privação de ÁguaRESUMO
OBJECTIVE: There is emerging evidence that angiotensin stimulates adipocyte differentiation and lipogenesis. This study tested the hypothesis that inhibition of angiotensin II by treatment with an angiotensin-converting enzyme inhibitor, perindopril, would reduce fat mass in rats. DESIGN: After a 12-day baseline, rats were divided into two groups: one was untreated and the other received perindopril (1.2 mg kg(-1) per day) in drinking water for 26 days. SUBJECTS: In total, 16 male Sprague-Dawley rats aged 10 weeks at the start of the study. MEASUREMENTS: Plasma leptin was measured in samples collected at baseline, half-way through and at the end of treatment. Body weight, food and water intake were measured daily throughout the experiment. Body fat mass, bone and lean mass were determined by dual energy X-ray absorptiometry (DEXA) at the end of the treatment period. RESULTS: Daily food intake was the same in both groups throughout the study. By the end of treatment, animals receiving perindopril showed a modest reduction in weight gain relative to the untreated animals (62.4+/-5.0 g vs 73.0+/-4.0 g; P<0.05). DEXA analysis showed that body composition was greatly altered and the perindopril-treated group had 26% less body fat mass than the untreated group (61.0+/-5.2 g vs 44.4+/-4.2 g; P<0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (P<0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64+/-0.56 ng ml(-1)) compared to the untreated group (8.27+/-1.03 ng ml(-1); P<0.001). In contrast, there were no differences in lean or bone mass between the two groups. CONCLUSION: Oral treatment with perindopril selectively reduced body fat mass without influencing daily food intake. In contrast, there were no differences in lean or bone mass between the two groups.
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Tecido Adiposo/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Leptina/sangue , Perindopril/farmacologia , Absorciometria de Fóton , Animais , Composição Corporal , Peso Corporal , Densidade Óssea , Ingestão de Alimentos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
To establish the effect of dietary omega-3 PUFA on angiotensin II (ANG II)-mediated hypertension, male TGR (mRen-2)27 (Ren-2) rats (animals with high ANG II activity) were maintained on a diet either deficient or sufficient in omega-3 PUFA from conception. Half the animals on each diet were treated with the angiotensin-converting enzyme inhibitor, perindopril, from birth. Ren-2 rats fed the omega-3 PUFA deficient diet were significantly more hypertensive than those fed the omega-3 PUFA sufficient diet. Perindopril reduced the blood pressure of both omega-3 PUFA-deficient and omega-3 PUFA-sufficient diet-fed Ren-2 rats. Body weight, body fat and plasma leptin were reduced by perindopril treatment but not affected by omega-3 PUFA supply. Given that the elevated blood pressure of the Ren-2 rat is mediated by ANG II, the data suggest that omega-3 PUFA may reduce hypertension via the renin-angiotensin system.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Ácidos Graxos Ômega-3/administração & dosagem , Hipertensão/terapia , Perindopril/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Angiotensina II/sangue , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/dietoterapia , Hipertensão/tratamento farmacológico , Masculino , Ratos , Renina/sangueRESUMO
1. Many mammals maintain a constant core body temperature in the face of a heat load by using evaporative cooling responses, such as sweating, panting and spreading of saliva. These cooling mechanisms incur a body fluid deficit if the fluid lost as sweat, saliva or respiratory moisture is not replaced by the ingestion of water; body fluid hypertonicity and hypovolaemia result. 2. Evidence in several mammals shows that, as they become dehydrated, evaporative cooling mechanisms such as sweating and panting are inhibited so that further fluid loss from the body is reduced. As a result, core temperature in the dehydrated animal is maintained at a higher than normal level. 3. Increasing the osmotic pressure of plasma has an inhibitory effect on panting and sweating in mammals. It has been proposed that osmoreceptors mediate these inhibitory influences of plasma hypertonicity on sweating and panting. 4. The suppression of panting in dehydrated sheep is mediated by cerebral osmoreceptors that are probably located in the lamina terminalis. We speculate that osmoreceptors in the lamina terminalis may also influence thermoregulatory sweating. 5. When dehydrated animals drink water, sweating and panting resume rapidly before water has been absorbed from the gut. It is likely that the act of drinking initiates a reflex that can override the osmoreceptor inhibition of panting, resulting in core temperature falling back quickly to a normal level.
Assuntos
Regulação da Temperatura Corporal/fisiologia , Mamíferos/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Desidratação , Ingestão de Líquidos , Homeostase , Humanos , Água/metabolismoRESUMO
A significant proportion of aged humans may have impaired thirst and inadequate fluid intake after a period of fluid deprivation. We have studied the water drinking responses, relative to body weight, of Munich Wistar (MW) rats in response to osmotic, hypovolemic, dehydrational, and angiotensin (Ang)-related stimuli as they aged from 3 to 24 months. Young 3-months-old (m.o.) rats had the largest daily fluid intakes and drinking responses to hypertonic and dehydrational stimuli, suggesting that they have accentuated thirst in comparison with older age groups. There were no differences in daily fluid intake from 6-24 m.o.; however, drinking responses to i.p. injection of hypertonic 0.4 mol/liter NaCl gradually declined over this period so that in 24-m.o. rats the response was only half that of 6-m.o. rats. Water intake after 24-h water deprivation also declined gradually over 24 months. Drinking responses to hypovolemia induced by s.c. injection of colloid (polyethylene glycol) were unchanged in 6- to 15-m.o. rats, then declined precipitously in 18- to 24-m.o. rats. Drinking responses to s.c. Ang II or s.c. isoproterenol were not reduced in 24-m.o. rats, nor was the drinking associated with feeding. Therefore, there are specific impairments of water intake in response to hypertonicity and hypovolemia in aged MW rats, but Ang-related drinking is not reduced. Like aged humans, aged MW rats exhibit high plasma atrial natriuretic peptide levels and impaired cardiovascular reflexes that could contribute to the impairment of thirst with age.
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Envelhecimento/fisiologia , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Hipovolemia/fisiopatologia , Isoproterenol/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Peso Corporal , Desidratação/fisiopatologia , Ingestão de Alimentos , Alemanha , Injeções Intraperitoneais , Ratos , Ratos Wistar , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/farmacologia , Fatores de TempoRESUMO
This study provides evidence that amylin acts centrally to increase sodium excretion in the sheep. Amylin was infused at 8 mg/h into a carotid artery (IC), via a lateral ventricle (ICV), intravenously (IV) or intra-renally (IR) into conscious sheep (n=5 per group). Renal sodium excretion increased by at least 3-fold after 1 h of amylin infusion by ICV (66+/-14 to 367+/-35 mmol/min) and IC (78+/-14 to 244+/-22 mmol/min) routes of administration. Amylin infusion IV caused a 1.5-fold increase in sodium excretion while IR infusion did not have a significant effect. The natriuretic effect of ICV infused amylin was blocked by pre-treatment with the angiotensin AT1 receptor antagonist, losartan (1 mg/h). No changes in blood pressure or heart rate were recorded at this dose of amylin by any route of administration. Plasma renin concentration increased (1.32+/-0.22 to 2.55+/-0.73 pmol/Ang I/h; P<0.05) following IR infusion of amylin, and remained unchanged when amylin was infused by the other routes of administration. We conclude that amylin causes changes in sodium excretion in sheep through a central, angiotensin-dependent pathway and that amylin may increase renin secretion by a direct effect on the kidney.
Assuntos
Amiloide/química , Angiotensinas/metabolismo , Amiloide/fisiologia , Animais , Pressão Sanguínea , Carboidratos/química , Artérias Carótidas/patologia , Eletrólitos , Feminino , Frequência Cardíaca , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Rim/metabolismo , Losartan/metabolismo , Losartan/farmacologia , Natriurese , Receptor Tipo 1 de Angiotensina/química , Renina/sangue , Renina/metabolismo , Ovinos , Sódio/metabolismo , Sódio/urina , Fatores de TempoRESUMO
Thirst motivates animals to seek fluid and drink it. It is regulated by the central nervous system and arises from neural and chemical signals from the periphery interacting in the brain to stimulate a drive to drink. Our research has focussed on the lamina terminalis and the manner in which osmotic and hormonal stimuli from the circulation are detected by neurons in this region and how that information is integrated with other neural signals to generate thirst. Our studies of osmoregulatory drinking in the sheep and rat have produced evidence that osmoreceptors for thirst exist in the dorsal cap of the organum vasculosum of the lamina terminalis (OVLT) and in the periphery of the subfornical organ, and possibly also in the median preoptic nucleus. In the rat, the hormones angiotensin II and relaxin act on neurons in the periphery of the subfornical organ to stimulate drinking. Studies of human thirst using functional magnetic resonance imaging (fMRI) techniques show that systemic hypertonicity activates the lamina terminalis and the anterior cingulate cortex, but the neural circuitry that connects sensors in the lamina terminalis to cortical regions subserving thirst remains to be determined. Regarding pathophysiological influences on thirst mechanisms, both excessive (polydipsia) and inadequate (hypodisia) water intake may have dire consequences. One of the most common primary polydipsias is that observed in some cases of schizophrenia. The neural mechanisms causing the excessive water intake in this disorder are unknown, so too are the factors that result in impaired thirst and inadequate fluid intake in some elderly humans.
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Ingestão de Líquidos/fisiologia , Sede/fisiologia , Animais , Hormônios/fisiologia , Humanos , Motivação , Vias Neurais/fisiologia , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
The lamina terminalis, located in the anterior wall of the third ventricle, is comprised of the subfornical organ, median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT). The subfornical organ and OVLT are two of the brain's circumventricular organs that lack the blood-brain barrier, and are therefore exposed to the ionic and hormonal environment of the systemic circulation. Previous investigations in sheep and rats show that this region of the brain has a crucial role in osmoregulatory vasopressin secretion and thirst. The effects of lesions of the lamina terminalis, studies of immediate-early gene expression and electrophysiological data show that all three regions of the lamina terminalis are involved in osmoregulation. There is considerable evidence that physiological osmoreceptors subserving vasopressin release are located in the dorsal cap region of the OVLT and possibly also around the periphery of the subfornical organ and in the MnPO. The circulating peptide hormones angiotensin II and relaxin also have access to peptide specific receptors (AT(1) and LGR7 receptors, respectively) in the subfornical organ and OVLT, and both angiotensin II and relaxin act on the subfornical organ to stimulate water drinking in the rat. Studies that combined neuroanatomical tracing and detection of c-fos expression in response to angiotensin II or relaxin suggest that both of these circulating peptides act on neurones within the dorsal cap of the OVLT and the periphery of the subfornical organ to stimulate vasopressin release.
Assuntos
Hipotálamo/metabolismo , Hipotálamo/fisiologia , Vasopressinas/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Órgão Subfornical/metabolismo , Órgão Subfornical/fisiologiaRESUMO
Angiotensinogen, the precursor molecule for angiotensins I, II and III, and the enzymes renin, angiotensin-converting enzyme (ACE), and aminopeptidases A and N may all be synthesised within the brain. Angiotensin (Ang) AT(1), AT(2) and AT(4) receptors are also plentiful in the brain. AT(1) receptors are found in several brain regions, such as the hypothalamic paraventricular and supraoptic nuclei, the lamina terminalis, lateral parabrachial nucleus, ventrolateral medulla and nucleus of the solitary tract (NTS), which are known to have roles in the regulation of the cardiovascular system and/or body fluid and electrolyte balance. Immunohistochemical and neuropharmacological studies suggest that angiotensinergic neural pathways utilise Ang II and/or Ang III as a neurotransmitter or neuromodulator in the aforementioned brain regions. Angiotensinogen is synthesised predominantly in astrocytes, but the processes by which Ang II is generated or incorporated in neurons for utilisation as a neurotransmitter is unknown. Centrally administered AT(1) receptor antagonists or angiotensinogen antisense oligonucleotides inhibit sympathetic activity and reduce arterial blood pressure in certain physiological or pathophysiological conditions, as well as disrupting water drinking and sodium appetite, vasopressin secretion, sodium excretion, renin release and thermoregulation. The AT(4) receptor is identical to insulin-regulated aminopeptidase (IRAP) and plays a role in memory mechanisms. In conclusion, angiotensinergic neural pathways and angiotensin peptides are important in neural function and may have important homeostatic roles, particularly related to cardiovascular function, osmoregulation and thermoregulation.
Assuntos
Astrócitos/fisiologia , Encéfalo/fisiologia , Sistema Renina-Angiotensina/fisiologia , Animais , Astrócitos/metabolismo , Encéfalo/metabolismo , Humanos , Peptidil Dipeptidase A/metabolismo , Renina/metabolismoRESUMO
Angiotensinogen, the precursor molecule of the peptides angiotensin I, II, and III, is synthesized in the brain and the liver. Evidence is reviewed that angiotensin II, and possibly angiotensin III, that are generated within the brain act within neural circuits of the central nervous system to regulate body fluid balance. Immunohistochemical studies in the rat brain have provided evidence of angiotensin-containing neurons, especially in the hypothalamic paraventricular nucleus, subfornical organ, periventricular region, and nucleus of the solitary tract, as well as in extensive angiotensin-containing fiber pathways. Angiotensin immunoreactivity is observed by electron microscope in synaptic vesicles in several brain regions, the most prominent of these being the central nucleus of the amygdala. Neurons in many parts of the brain (lamina terminalis, paraventricular and parabrachial nuclei, ventrolateral medulla, and nucleus of the solitary tract) known to be involved in the regulation of body fluid homeostasis exhibit angiotensin receptors of the AT(1) subtype. Pharmacological studies in several species show that intracerebroventricular administration of AT(1) receptor antagonist drugs inhibit homeostatic responses to the central administration of hypertonic saline, intravenous infusion of the hormone relaxin, or thermal dehydration. Responses affected by centrally administered AT(1) antagonists are water drinking, vasopressin secretion, natriuresis, increased arterial pressure, reduced renal renin release, salt hunger, and thermoregulatory adjustments. We conclude that angiotensinergic neural pathways in the brain probably have an important homeostatic function, especially in regard to osmoregulation and thermoregulation, and the maintenance of arterial pressure.
Assuntos
Angiotensina III/farmacologia , Angiotensina II/farmacologia , Encéfalo/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Pressão Sanguínea/fisiologia , Regulação da Temperatura Corporal , Desidratação , Comportamento de Ingestão de Líquido , Homeostase , Humanos , Rim/fisiologia , Neurônios/fisiologia , Receptores de Angiotensina/fisiologia , Renina/farmacologia , Vesículas Sinápticas , Vasopressinas/farmacologiaAssuntos
Regulação da Temperatura Corporal/fisiologia , Hipotálamo/fisiologia , Glândula Sublingual/fisiologia , Glândula Submandibular/fisiologia , Transmissão Sináptica , Animais , Denervação , Herpesvirus Suídeo 1 , Hipotálamo/virologia , Modelos Animais , Prosencéfalo/fisiologia , Prosencéfalo/virologia , Ratos , Salivação/fisiologia , Glândula Sublingual/inervação , Glândula Sublingual/virologia , Glândula Submandibular/inervação , Glândula Submandibular/virologia , Equilíbrio HidroeletrolíticoRESUMO
We investigated the effect of ruminal water loading before feeding on the natriuretic and drinking responses that follow feeding. Six sheep fed 800 g of chaff drank 1360 +/- 150 mL during the 5 h immediately following feeding and increased renal Na excretion. Plasma Na concentration increased by 4 mmol L (-1) and plasma osmolality by 9 mosmol kg (-1) within 1.5 h and remained elevated. A rumen load of water administered before feeding prevented the increases in plasma Na and osmolality without affecting feeding. The natriuresis, water drinking and vasopressin secretion in response to feeding were abolished. Total sodium excreted during the experiment was halved in water-loaded animals compared with untreated animals (30.4 +/- 2.1 mmol (-1) cf. 63.8 +/- 2.9 mmol-1; P < 0.01). Ruminal loading with isotonic saline caused a 33% reduction in postprandial drinking, however, reducing cerebrospinal fluid NaCl concentration abolished postprandial drinking and natriuresis. Intravenous infusion of isotonic dextran appeared to delay the onset of water intake without changing the total volume of water drunk, suggesting a role of plasma volume in initiating drinking. We conclude from the data that central osmoregulatory mechanisms that include increased sodium excretion as well as thirst and vasopressin release are activated following food intake by sheep.