RESUMEN
Overweight and obesity are a worldwide pandemic affecting billions of people. These conditions have been associated with a chronic low-grade inflammatory state that is recognized as a risk factor for a range of somatic diseases as well as neurodevelopmental disorders, anxiety disorders, trauma- and stressor-related disorders, and affective disorders. We previously reported that the ingestion of a high-fat diet (HFD; 45% fat kcal/g) for nine weeks was capable of inducing obesity in rats in association with increased reactivity to stress and increased anxiety-related defensive behavior. In this study, we conducted a nine-week diet protocol to induce obesity in rats, followed by investigation of anxiety-related defensive behavioral responses using the elevated T-maze (ETM), numbers of FOS-immunoreactive cells after exposure of rats to the avoidance or escape task of the ETM, and neuroinflammatory cytokine expression in hypothalamic and amygdaloid nuclei. In addition, we investigated stress-induced cutaneous thermoregulatory responses during exposure to an open-field (OF). Here we demonstrated that nine weeks of HFD intake induced obesity, in association with increased abdominal fat pad weight, increased anxiety-related defensive behavioral responses, and increased proinflammatory cytokines in hypothalamic and amygdaloid nuclei. In addition, HFD exposure altered avoidance- or escape task-induced FOS-immunoreactivity within brain structures involved in control of neuroendocrine, autonomic, and behavioral responses to aversive stimuli, including the basolateral amygdala (BLA) and dorsomedial (DMH), paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. Furthermore, rats exposed to HFD, relative to control diet-fed rats, responded with increased tail skin temperature at baseline and throughout exposure to an open-field apparatus. These data are consistent with the hypothesis that HFD induces neuroinflammation, alters excitability of brain nuclei controlling neuroendocrine, autonomic, and behavioral responses to stressful stimuli, and enhances stress reactivity and anxiety-like defensive behavioral responses.
Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Dieta Alta en Grasa/efectos adversos , Neuroinmunomodulación/fisiología , Amígdala del Cerebelo/metabolismo , Animales , Ansiedad/metabolismo , Trastornos de Ansiedad/metabolismo , Corticosterona , Hipotálamo/metabolismo , Masculino , Obesidad , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Aumento de PesoRESUMEN
There is ample evidence that both lateral/dorsolateral periaqueductal gray (l/dlPAG) and basolateral amygdala (BLA) are essential for the regulation of the autonomic responses evoked during innate reactions to threatening stimuli. However, it is not well established to what extent the BLA regulates the upstream functional connection from the l/dlPAG. Here we evaluated the role of the BLA and its glutamatergic receptors in the cardiovascular responses induced by l/dlPAG stimulation in rats. We examined the influence of acute inhibition of the BLA, unilaterally, by injecting muscimol on the cardiovascular responses evoked by the injection of N-methyl D-aspartate (NMDA) into the l/dlPAG. We also evaluated the role of BLA ionotropic glutamate receptors in these responses by injecting antagonists of NMDA and AMPA/kainate receptor subtypes into the BLA. Our results show that the microinjection of NMDA in the BLA increased the mean arterial pressure (MAP) and heart rate (HR). Injection of NMDA into the l/dlPAG caused similar increases in these variables, which was prevented by the prior injection of muscimol, a GABAA agonist, into the BLA. Moreover, injection of glutamatergic antagonists (2-amino-5-phosphonopentanoate (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) into the BLA reduced the increase in MAP and HR induced by l/dlPAG activation. Finally, the inhibition of the central amygdala neurons failed to reduce the cardiovascular changes induced by l/dlPAG activation. These results indicate that physiological responses elicited by l/dlPAG activation require the neuronal activity in the BLA. This ascending excitatory pathway from the l/dlPAG to the BLA might ensure the expression of the autonomic component of the defense reaction.
Asunto(s)
Amígdala del Cerebelo/fisiología , Presión Arterial/fisiología , Frecuencia Cardíaca/fisiología , Neuronas/fisiología , Sustancia Gris Periacueductal/fisiología , Receptores de Glutamato/metabolismo , 2-Amino-5-fosfonovalerato/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Presión Arterial/efectos de los fármacos , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Agonistas de Receptores de GABA-A/farmacología , Ácido Glutámico/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Microinyecciones , Muscimol/farmacología , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Sustancia Gris Periacueductal/efectos de los fármacos , Ratas Wistar , Receptores de GABA-A/metabolismoRESUMEN
This study aimed to evaluate the cardiovascular component of the arterial chemoreflex in rats recovered from low protein diet. Male Fischer rats were randomly divided into control and recovered (R-PR) groups after weaning. R-PR rats were fed with low protein diet for 35days and recovered under normal protein diet for 70days. Control rats received normal protein diet for 105days. Arterial chemoreflex was elicited by intravenous injection of KCN. Results showed that pressor response of the chemoreflex was increased in R-PR. Data suggest that protein restriction may alter cardiovascular response to chemical activation of the chemoreflex after recovery.
Asunto(s)
Barorreflejo/fisiología , Presión Sanguínea/fisiología , Dieta con Restricción de Proteínas/efectos adversos , Frecuencia Cardíaca/fisiología , Desnutrición/fisiopatología , Animales , Masculino , Distribución Aleatoria , Ratas Endogámicas F344RESUMEN
Rats fed a high-fat diet (HFD) present an exaggerated endocrine response to stress conditions, which, like obesity, show a high correlation with cardiovascular diseases. Meanwhile the GABAergic neurotransmission within the dorsomedial hypothalamus (DMH) is involved in the regulation of the physiological responses during emotional stress. Here we evaluated the influence of obesity, induced by a HFD, on the cardiovascular responses induced by air jet stress in rats, and the role of the GABAergic tonus within the DMH in these changes. Our results showed that consumption of a HFD (45% w/w fat) for 9 weeks induced obesity and increases in baseline mean arterial pressure (MAP) and heart rate (HR). Moreover, obesity potentiated stress responsiveness, evidenced by the greater changes in MAP and HR induced by stress in obese rats. The injection of muscimol into the DMH reduced the maximal increases in HR and MAP induced by stress in both groups; however, the reduction in the maximal increases in MAP in the HFD group was less pronounced. Moreover, the injection of muscimol into the DMH of obese rats was less effective in reducing the stress-induced tachycardia, since the HR attained the same levels at the end of the stress paradigm as after the vehicle injection. Injection of bicuculline into DMH induced increases in MAP and HR in both groups. Nevertheless, obesity shortened the tachycardic response to bicuculline injection. These data show that obesity potentiates the cardiovascular response to stress in rats due to an inefficient GABAA-mediated inhibition within the DMH.
Asunto(s)
Presión Arterial/fisiología , Dieta Alta en Grasa/efectos adversos , Frecuencia Cardíaca , Obesidad/fisiopatología , Receptores de GABA-A/metabolismo , Estrés Psicológico/fisiopatología , Ácido gamma-Aminobutírico/metabolismo , Animales , Presión Arterial/efectos de los fármacos , Bicuculina/farmacología , Emociones , Agonistas de Receptores de GABA-A/farmacología , Antagonistas de Receptores de GABA-A/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Muscimol/farmacología , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Estimulación Física , Ratas , Ratas Wistar , Estrés Psicológico/complicaciones , Estrés Psicológico/tratamiento farmacológico , Taquicardia/tratamiento farmacológico , Taquicardia/etiología , Taquicardia/fisiopatología , Factores de TiempoRESUMEN
Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 microg/kg) or sodium nitroprusside (1.0 to 10.0 microg/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 +/- 0.74 and -7.93 +/- 1.08 bpm/mmHg, respectively). The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 +/- 0.3 sham vs -3.6 +/- 0.2 bpm/mmHg) 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity.
Asunto(s)
Barorreflejo/efectos de los fármacos , Deferoxamina/farmacología , Quelantes del Hierro/farmacología , Sobrecarga de Hierro/fisiopatología , Animales , Barorreflejo/fisiología , Presión Sanguínea/efectos de los fármacos , Estado de Conciencia , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Nitroprusiato/farmacología , Ratas , Ratas Endogámicas F344RESUMEN
The correlation between nutrition and cardiovascular related disorders is a well-established fact. Previous work from our Laboratory has suggested a significant compromise of cardiovascular reflexes in conscious rats submitted to a low-protein (LP) diet. Our working hypothesis is that the basal level of mean arterial pressure (MAP), variability of the mean arterial pressure (VMAP), heart rate (HR) and variability of heart rate (VHR) are altered in rats submitted to a protein restricted diet. Two experimental groups were used: control group (normal protein 15%, NP) and malnourished group (low-protein 6%, LP). In order to verify the efficiency of the dietary restriction we measured body weight, total blood protein, plasma albumin, urea and glucose. Our experiments demonstrated that the malnourished rats presented augment levels of basal MAP (LP 122+/-2 mmHg vs. NP 113+/-1 mmHg) and of VMAP (LP 12.8+/-1.5mmHg vs. NP 9+/-1mmHg) when compared to the control group. We observed similar increased levels, in the malnourished group, for both HR (LP 429+/-8 bpm vs. NP 381+/-7bpm) and VHR (LP 67.6+/-8.3bpm vs. NP 44.4+/-4.9bpm). Our results suggest a correlation between the LP diet in Fisher rats and the increased basal levels of mean arterial pressure, HR and their respective variability.
Asunto(s)
Presión Sanguínea/fisiología , Dieta con Restricción de Proteínas/efectos adversos , Frecuencia Cardíaca/fisiología , Animales , Peso Corporal , Encéfalo/anatomía & histología , Masculino , Tamaño de los Órganos , Deficiencia de Proteína/fisiopatología , RatasRESUMEN
The present study evaluated the effects of a low-protein diet (LP, 6% protein) on cardiovascular reflexes of Male Fisher rats. Three experimental groups, and their respective controls (15% protein), were used: (1) Baroreceptor reflex (BAR); (2) Bezold-Jarisch reflex (BJR); and (3) Prazosin treated. Dietary restriction began after weaning (three weeks) and lasted for a period of five weeks, after which animals were subjected to the experimental protocols. The BAR group was evaluated through injections of phenylephrine (0.5-5.0 microgram/Kg, i.v.) and sodium nitroprusside (0.7-7.0 microgram/Kg, i.v.) while the BJR was evaluated through injections of serotonin (2.5-10 microgram/Kg, i.v.). Our results showed an increased baroreflex gain bradycardia for the LP group (-0.96+/-0.34 vs. -2.12+/-1.06 bpm/mmHg) and a larger bradycardia for the BJR the LP group (160+/-18% greater than controls). Basal cardiovascular parameters were not different between LP and control rats, however LP animals treated with prazosin resulted in a larger fall of blood pressure (-19+/-3 vs. -28+/-5 mmHg). In conclusion, LP rats present an increased responsiveness of BAR and BJR, which could contribute to their normal levels of cardiovascular parameters, in spite of the possible increase in the sympathetic vasomotor tonus observed with the prazosin protocol.
Asunto(s)
Barorreflejo/fisiología , Presión Sanguínea/fisiología , Dieta con Restricción de Proteínas , Corazón/efectos de los fármacos , Tono Muscular/fisiología , Prazosina/farmacología , Vías Aferentes/efectos de los fármacos , Vías Aferentes/fisiología , Animales , Presión Sanguínea/efectos de los fármacos , Peso Corporal , Fenómenos Fisiológicos Cardiovasculares/efectos de los fármacos , Modelos Animales de Enfermedad , Corazón/fisiopatología , Masculino , Tono Muscular/efectos de los fármacos , Nitroprusiato/farmacología , Fenilefrina/farmacología , Presorreceptores/efectos de los fármacos , Presorreceptores/fisiología , Ratas , Ratas Endogámicas F344 , Serotonina/farmacologíaRESUMEN
The distribution of cocaine- and amphetamine-regulated transcript-like immunoreactivity (CART-LI) was investigated in the rat spinal cords with the use of an antiserum against the CART peptide fragment 55-102. CART-LI fibers were concentrated in the superficial layers of the dorsal horn of all segments. In addition to CART-LI fibers, intensely labeled somata were detected in the intermediolateral cell column (IML) and other sympathetic preganglionic nuclei of the thoracolumbar segments. In the lumbosacral segments, CART-LI fibers but not somata were seen in the sacral parasympathetic nucleus. Double-labeling the spinal sections with choline acetyltransferase (ChAT)-antisera and CART-antisera revealed that the large majority of ChAT-positive somata in the sympathetic preganglionic nuclei were CART-positive, whereas ChAT-positive somata in the parasympathetic preganglionic nuclei were CART-negative. Our results show that CART-LI is selectively expressed in a population of sympathetic preganglionic neurons (SPNs), but not in parasympathetic preganglionic neurons (PPNs) of the rat.
Asunto(s)
Proteínas del Tejido Nervioso/metabolismo , Médula Espinal/metabolismo , Animales , Femenino , Ganglios Parasimpáticos/metabolismo , Ganglios Simpáticos/metabolismo , Región Lumbosacra , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The Bezold-Jarisch (B-J) reflex was activated by serotonin (5-HT, i.v.) before and 10 min after bilateral microinjection of increasing doses of kynurenic acid, a non-selective antagonist of excitatory amino acid (EAA) receptors, into the commissural nucleus tractus solitarii (NTS) of sino-aortic deafferentated (SAD) and sham-operated (SO) unanesthetized rats. Increasing doses of kynurenic acid produced a dose-dependent blockade of the bradycardic and hypotensive responses to B-J reflex activation in both SO (from 0.1 to 10.0 nmol/100 nl) and SAD (from 0.1 to 2.0 nmol/100 nl). Comparison of the effect of kynurenic acid on the hypotension and bradycardic dose-response curves showed a significant difference between SO and SAD rats, indicating that smaller doses of kynurenic acid are required in SAD rats than in SO rats to block the neurotransmission of the B-J reflex in the NTS. The data also showed that bilateral microinjection of kynurenic acid into the NTS at doses of 0.5 (131 +/- 7 vs. 115 +/- 8 mmHg) and 2.0 nmol/100 nl (140 +/- 11 vs. 116 +/- 9 mmHg) produced an acute and significant increase in the basal mean arterial pressure of SAD rats similar to that observed with the same doses in SO rats, which was back to control values 5-10 min later. The increase in basal mean arterial pressure immediately after kynurenic acid microinjection into the NTS of SAD rats suggests that in the absence of the arterial baroreceptors, the B-J reflex plays an important role in the autonomic regulation of the circulation. The data also show different dose-response curves for hypotension and bradycardia in response to B-J reflex activation in SAD than in SO rats in the presence of increasing doses of kynurenic acid into the NTS, indicating that the neurotransmission of the B-J reflex in the NTS of SAD rats is more sensitive to the blockade of the EAA receptors than in SO rats.
Asunto(s)
Fenómenos Fisiológicos Cardiovasculares , Desnervación , Reflejo/fisiología , Seno Aórtico/inervación , Núcleo Solitario/fisiología , Transmisión Sináptica , Vías Aferentes/fisiología , Animales , Presión Sanguínea/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Antagonistas de Aminoácidos Excitadores/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Ácido Quinurénico/farmacología , Masculino , Ratones , Microinyecciones , Ratas , Ratas Wistar , Serotonina/farmacologíaRESUMEN
The purpose of the present study was to evaluate whether or not cardiovagal excitatory and sympatho-inhibitory pathways of the Bezold-Jarisch reflex at the NTS level were mediated by NMDA receptors. The Bezold-Jarisch reflex was activated by intravenous (i.v.) injection of serotonin in conscious rats before and after microinjection of phosphonovaleric acid (AP-5) a selective NMDA antagonist, into the NTS. The Bezold-Jarisch reflex was also activated before and after methyl-atropine (i.v.) in order to evaluate if the changes in mean arterial pressure were dependent on the bradycardic response. The data showed that AP-5 into the NTS produced a dose-dependent reduction in both bradycardic and hypotensive responses to activation of the Bezold-Jarisch reflex. Methyl-atropine also blocked the bradycardic and hypotensive responses to Bezold-Jarisch reflex activation. The data show that in conscious rats the cardiovagal component of the Bezold-Jarisch reflex plays a major role in the cardiovascular changes produced by the activation of this reflex and suggest that the neurotransmission of the cardiovagal component of the Bezold-Jarisch reflex is mediated by NMDA receptors.
Asunto(s)
N-Metilaspartato/antagonistas & inhibidores , Reflejo/efectos de los fármacos , Núcleo Solitario/fisiología , Sistema Nervioso Simpático/efectos de los fármacos , 2-Amino-5-fosfonovalerato/farmacología , Anestesia por Inhalación , Animales , Presión Sanguínea/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Microinyecciones , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/fisiología , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/farmacología , Núcleo Solitario/anatomía & histología , Transmisión Sináptica/efectos de los fármacosRESUMEN
Activation of carotid chemoreceptors with intravenous potassium cyanide (KCN) produces increases in arterial pressure, bradycardia, and tachypnea. In the present study, we activated carotid chemoreceptors with KCN and the neurotransmission of the chemoreceptor reflex into the commissural nucleus tractus solitarii (NTS) was blocked with phosphonovaleric acid (AP-5), an N-methyl-D-aspartate (NMDA)-selective antagonist. The aim of this study was to evaluate the involvement of NMDA receptors in the cardiovascular and respiratory responses produced by chemoreceptor activation in unanesthetized rats. The pressor response to KCN was not changed after microinjection of three different doses of AP-5 into the NTS, whereas the bradycardic response was reduced in a dose-dependent manner. The increase in respiratory frequency in response to carotid chemoreceptor activation was also not affected by AP-5 microinjected into the NTS. The data indicate that the activation of the cardiovagal component of the chemoreflex in the commissural NTS is mediated by NMDA receptors, whereas pressor and ventilatory responses are not.