RESUMO
Heart failure (HF) is a complex syndrome that involves changes in behavioral, neural and endocrine regulatory systems. Dietary salt restriction along with pharmacotherapy is considered an essential component in the effective management of symptomatic HF patients. However, it is well recognized that HF patients typically have great difficulty in restricting sodium intake. We hypothesized that under HF altered activity in systems that normally function to regulate body fluid and cardiovascular homeostasis could produce an increased preference for the taste of salt. Therefore, this study was conducted to evaluate the perceived palatability (defined as salt preference) of food with different concentrations of added salt in compensated chronically medicated HF patients and comparable control subjects. Healthy volunteers (n=25) and medicated, clinically stable HF patients (n=38, NYHA functional class II or III) were interviewed and given an evaluation to assess their preferences for different amounts of saltiness. Three salt concentrations (0.58, 0.82, and 1.16 g/100 g) of bean soup were presented to the subjects. Salt preference for each concentration was quantified using an adjective scale (unpleasant, fair or delicious). Healthy volunteers preferred the soup with medium salt concentration (p=0.042), HF patients disliked the low concentration (p<0.001) and preferred the high concentration of salted bean soup (p<0.001). When compared to healthy volunteers, HF patients demonstrated a significantly greater preference for the soup with a high salt concentration (p=0.038). It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt.
Assuntos
Comportamento de Escolha , Comportamento Alimentar/psicologia , Preferências Alimentares/psicologia , Insuficiência Cardíaca/fisiopatologia , Cloreto de Sódio na Dieta , Estudos de Casos e Controles , Feminino , Alimentos , Humanos , Intenção , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Paladar , Percepção Gustatória/fisiologiaRESUMO
Bilateral injections of moxonidine, an α2-adrenoceptor and imidazoline receptor agonist, into the lateral parabrachial nuclei (LPBN) enhance sodium appetite induced by extracellular dehydration. In the present study, we examined whether LPBN moxonidine treatments change taste reactivity to hypertonic NaCl solution administered into the mouth by intra-oral (IO) cannula. Male Holtzman rats prepared with IO and bilateral LPBN cannulas received subcutaneous injections of furosemide (FURO; 10 mg/kg) and captopril (CAP; 5 mg/kg) to induce hypovolemia with mild hypotension and an accompanying salt appetite and thirst before testing the taste reactivity to oral infusions of 0.3 M NaCl (1.0 ml/min). In the first experiment 45 min after subcutaneous injections of FURO+CAP or vehicle, moxonidine was bilaterally injected into the LPBN, and then 15 min later both bodily and oral-facial ingestive and rejection responses to 0.3 M NaCl delivered through the IO cannula were assessed. Both LPBN vehicle and moxonidine treated rats showed increased ingestive and decreased rejection responses to the IO hypertonic solution. The IO 0.3 M NaCl infusion-evoked ingestive and rejection taste related behaviors were comparable in the LPBN vehicle- vs. the LPBN moxonidine-injected groups. In a second experiment, rats received the same FURO+CAP treatments and LPBN injections. However, beginning 15 min after the LPBN injections, they were given access to water and 0.3M NaCl and were allowed to consume the fluids for most of the next 60 min with the free access intake being interrupted only for a few minutes at 15, 30 and 60 min after the fluids became available. During each of these three brief periods, a taste reactivity test was conducted. On the three taste reactivity tests rats that received LPBN vehicle injections showed progressive declines in ingestive responses and gradual increases in rejection responses. However, in contrast to the LPBN vehicle treated rats, animals receiving bilateral injections of LPBN moxonidine maintained a high number of ingestive responses and a low number of rejection responses throughout the test period even in spite of evidencing substantial water and 0.3 M NaCl consumption during the periods of free access. The results suggest that after α2-adrenoceptor agonist delivery to the LPBN the acceptance of 0.3 M NaCl is sustained and the negative attributes of the solution are minimized. The maintained positive rewarding qualities of 0.3 M NaCl are likely to account for why LPBN moxonidine treated rats show such a remarkable salt appetite when assayed by the volume of hypertonic 0.3 M NaCl consumed.
Assuntos
Agonistas Adrenérgicos/farmacologia , Imidazóis/farmacologia , Ponte/efeitos dos fármacos , Solução Salina Hipertônica/administração & dosagem , Paladar/efeitos dos fármacos , Animais , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Diuréticos/farmacologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Vias de Administração de Medicamentos , Interações Medicamentosas , Furosemida/farmacologia , Masculino , Ponte/fisiologia , Ratos , Fatores de TempoRESUMO
Structures of the lamina terminalis (LT) sense and integrate information reflecting the state of body water and sodium content. Output from the LT projects into a neural network that regulates body fluid balance. Serotonin (5-HT) and the dorsal raphe nuclei (DRN) have been implicated in the inhibitory control of salt intake (i.e., sodium appetite). Signals arriving from the LT evoked by fluid depletion-induced sodium ingestion interact with this inhibitory serotonergic system. We investigated the role of neurons along the LT that directly project to the DRN. We analyzed the pattern of immunoreactivity (ir) of LT cells double-labeled for Fos (a marker of neural activity) and Fluorogold (FG; a retrograde tracer) following sodium depletion-induced sodium intake. Seven days after injection of FG into the DRN, sodium appetite was induced by furosemide injection and overnight access to only a low sodium diet (Furo-LSD) and distilled water. Twenty-four hours later, access to 0.3 M NaCl was given to depleted or sham-depleted rats and sodium intake was measured over the following 60 min. Ninety minutes after the termination of the intake test, the animals were perfused and their brains were processed for immunohistochemical detection of Fos and FG. Compared to sham-depleted animals there was a significantly greater number of Fos-/FG-ir double-labeled cells in the subfornical organ, the organum vasculosum of the lamina terminalis and the median preoptic nucleus in rats that ingested NaCl. Projections from the LT cells may contribute to inhibitory mechanisms involving 5-HT neurons in the DRN that limit the intake of sodium and prevent excess volume expansion.
Assuntos
Regulação do Apetite/fisiologia , Hipotálamo/metabolismo , Vias Neurais/metabolismo , Núcleos da Rafe/metabolismo , Cloreto de Sódio na Dieta/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Alostase/efeitos dos fármacos , Alostase/fisiologia , Animais , Regulação do Apetite/efeitos dos fármacos , Contagem de Células , Diuréticos/farmacologia , Alimentos Formulados , Furosemida/farmacologia , Hipotálamo/citologia , Hipotálamo/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Vias Neurais/citologia , Vias Neurais/efeitos dos fármacos , Área Pré-Óptica/citologia , Área Pré-Óptica/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Núcleos da Rafe/citologia , Núcleos da Rafe/efeitos dos fármacos , Ratos , Ratos Wistar , Resposta de Saciedade/efeitos dos fármacos , Resposta de Saciedade/fisiologia , Cloreto de Sódio na Dieta/farmacologia , Estilbamidinas , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
The objective of the present study was to conduct a short-term international course on translational physiology for medical students from Wright State University and the University of Iowa. The goals were to 1) provide students with an exposure to the academic, cultural, and medical environments in Brazil; 2) promote awareness of the global medical community; and 3) provide an academic course focused on translational physiology. An evaluation of the students was conducted to determine whether such a short-term course might be useful in the medical curriculum. The 2-wk course was held in the summer of 2005 at the University of São Paulo School of Medicine in Ribeirão Preto, Brazil, for 23 American students. The program included presentations of basic and clinical topics, meetings with medical students, and clinical presentations. The program finished with student attendance at a scientific meeting sponsored by the Brazilian Society of Hypertension. Student surveys evaluated issues related to perceived treatment, Brazilian medical school environment, culture and personal attributes, and career aspirations. The international Medical Sciences Translational Physiology course for medical students provided a brief, but intense, experience. It gave students a picture of the medical environment in Brazil and an appreciation for the differences and similarities in cultures. Most students reported that it was a positive experience that would be beneficial to their careers. In conclusion, a short-term international course provides an efficient means for medical students to experience aspects of global medical science.
Assuntos
Currículo , Difusão de Inovações , Educação Médica , Internacionalidade , Fisiologia/educação , Estudantes de Medicina , Brasil , Características Culturais , Currículo/normas , Humanos , Estados UnidosRESUMO
The present study investigated the role of corticotropin-releasing hormone (CRH) in the lateral parabrachial nucleus (LPBN) in the behavioral control of body fluid homeostasis by determining the effect of bilateral injections of the CRH receptor antagonist, alpha-helical corticotropin-releasing factor (CRF)(9-41), and the CRH receptor agonist, CRH, on sodium chloride (salt appetite) and water (thirst) intake. Groups of adult, male Sprague-Dawley rats had stainless-steel cannulas implanted bilaterally into the LPBN and were sodium depleted or water deprived. Bilateral injections of alpha-helical CRF(9-41) into the LPBN significantly potentiated water and salt intake in the sodium-depleted rats when access to fluids was restored. Bilateral injections of alpha-helical CRF(9-41) into the LPBN (1.0 microg) also increased sodium appetite in water-deprived rats. Conversely, in sodium-depleted animals, bilateral injections of CRH inhibited sodium chloride intake. These results suggest that there is an endogenous CRH inhibitory mechanism operating in the LPBN to modulate the intake of sodium (salt appetite). This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states.
Assuntos
Apetite/fisiologia , Hormônio Liberador da Corticotropina/fisiologia , Ingestão de Líquidos , Fragmentos de Peptídeos/fisiologia , Ponte/fisiologia , Cloreto de Sódio na Dieta , Animais , Hormônio Liberador da Corticotropina/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Furosemida/farmacologia , Masculino , Fragmentos de Peptídeos/farmacologia , Ponte/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidoresRESUMO
Previous studies using non-specific serotonergic agonists and antagonists have shown the importance of serotonergic inhibitory mechanisms in the lateral parabrachial nucleus (LPBN) for controlling sodium and water intake. In the present study, we investigated whether the serotonergic 5-HT(1A) receptor subtype in the LPBN participates in this control. Male Holtzman rats had cannulas implanted bilaterally into the LPBN. Bilateral injections of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.1, 1.25, and 2.5 microg/0.2 microl), into the LPBN enhanced 0.3 M NaCl and water intake of rats injected subcutaneously with the diuretic furosemide (10 mg/kg bw) and a low dose of the angiotensin-converting enzyme inhibitor, captopril (5 mg/kg bw). The increase in NaCl intake produced by 8-OH-DPAT injections was reduced in dose-related manner by pre-treating the LPBN with the selective 5-HT(1A) serotonergic antagonist, WAY-100635 (WAY, 1 and 2 microg/0.2 microl). In contrast, WAY did not affect water intake produced by 8-OH-DPAT. WAY-100635 injected alone into the LPBN had no effect on NaCl ingestion. Injections of 8-OH-DAPT (0.1 microg/0.2 microl) into the LPBN also increased 0.3 M NaCl intake induced by 24-h sodium depletion (furosemide, 20 mg/kg bw plus 24 h of sodium-free diet). Serotonin (5-HT, 20 mug/0.2 mul) injected alone or combined with 8-OH-DPAT into the LPBN reduced 24-h sodium depletion-induced 0.3 M NaCl intake. Therefore, the activation of serotonergic 5-HT(1A) receptors in the LPBN increases stimulated hypertonic NaCl and water intake, while 5-HT injections into the LPBN reduce NaCl intake and prevent the effects of serotonergic 5-HT(1A) receptor activation.
Assuntos
Ponte/fisiologia , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Cloreto de Sódio na Dieta , 8-Hidroxi-2-(di-n-propilamino)tetralina/administração & dosagem , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Apetite/efeitos dos fármacos , Captopril/administração & dosagem , Captopril/farmacologia , Diuréticos/administração & dosagem , Diuréticos/farmacologia , Furosemida/administração & dosagem , Furosemida/farmacologia , Injeções , Injeções Subcutâneas , Masculino , Piperazinas/administração & dosagem , Piperazinas/farmacologia , Piridinas/administração & dosagem , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/farmacologia , Sacarose/farmacologia , Privação de ÁguaAssuntos
Adenoviridae , Vetores Genéticos , Hipotálamo/metabolismo , Proteínas Luminescentes , Neuro-Hipófise/metabolismo , Animais , Animais Geneticamente Modificados , Células Cultivadas , Técnicas de Transferência de Genes , Genes Reporter/fisiologia , Marcadores Genéticos/fisiologia , Proteínas de Fluorescência Verde , RatosRESUMO
Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 +/- 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma Na+; 2) decreased blood volume; and 3) reduced total body Na+; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma Na+ concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water.
Assuntos
Apetite/fisiologia , Genes Precoces/fisiologia , Sódio na Dieta/farmacologia , Privação de Água/fisiologia , Animais , Pressão Sanguínea/fisiologia , Volume Sanguíneo/fisiologia , Ingestão de Líquidos/fisiologia , Hidratação , Hipovolemia/fisiopatologia , Masculino , Potássio/sangue , Área Pré-Óptica/química , Área Pré-Óptica/fisiologia , Proteínas Proto-Oncogênicas c-fos/análise , Ratos , Ratos Sprague-Dawley , Renina/sangue , Sódio/sangue , Órgão Subfornical/química , Órgão Subfornical/fisiologia , Núcleo Supraóptico/química , Núcleo Supraóptico/fisiologia , Sede/fisiologia , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
We evaluated serotonergic hindbrain groups of cells for their involvement in the generation and inhibition of sodium appetite. For that purpose, we analyzed the number of Fos-immunoreactive (Fos-ir) cells and double-labeled Fos-serotonin (5-HT)-ir neurons within different nuclei of the hindbrain raphe system and the area postrema (AP). Sodium depletion and sodium appetite were induced by peritoneal dialysis. Twenty-four hours after peritoneal dialysis, a 2% NaCl solution intake test was given to peritoneal dialyzed animals [PD-with access (PD-A) group] and to control dialyzed animals [CD-with access (CD-A) group]. Two additional groups of animals received either peritoneal dialysis or control dialysis but were not given access to the 2% NaCl [CD-no access (CD-NA) group or PD-no access (PD-NA) group]. The number of Fos-ir neurons within different nuclei of the raphe system was increased in spontaneous and induced sodium ingestion of CD-A and PD-A groups compared with the CD-NA and PD-NA groups. The PD-NA group had significantly fewer double-labeled cells along the raphe system compared with the animals in near-normal sodium balance (CD-NA and CD-A) or in the process of restoring sodium balance by consuming NaCl (PD-A). The AP of the PD-A group showed a significant increase in the number of Fos-ir and Fos-5-HT-ir cells compared with the PD-NA and CD groups. Our results suggest that serotonergic pathways with cell bodies in the AP and the raphe system are involved in the control of sodium appetite.