Papers by Eduardo Colombari
Frontiers in Physiology, 2022
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2000
The role of baroreceptors, cardiopulmonary receptors, and renal nerves in the cardiovascular adju... more The role of baroreceptors, cardiopulmonary receptors, and renal nerves in the cardiovascular adjustments to volume expansion (VE) with 4% Ficoll (Pharmacia; 1% body wt, 0.4 ml/min) were studied in urethan-anesthetized rats. In control animals, VE produced a transitory increase in mean arterial pressure (MAP), which peaked at 10 min (17 ± 4 mmHg) and increases in renal (128 ± 6 and 169 ± 19% of baseline at 10 and 40 min, respectively) and hindlimb vascular conductance (143 ± 6 and 150 ± 10%). These cardiovascular adjustments to VE were unaffected by bilateral vagotomy. After sinoaortic denervation, the increase in MAP induced by VE was greater than in control rats (30 ± 4 mmHg). However, renal vasodilation in response to VE was blocked, whereas hindlimb vasodilation was similar to that observed in control rats. After unilateral renal denervation (ipsilateral to flow recording), the initial renal vasodilation was blocked. However, 40 min after VE, a significant renal vasodilation (125...
American Journal of Physiology-Heart and Circulatory Physiology, 2001
In this study, we characterized the arterial pressure, heart rate, and regional vascular conducta... more In this study, we characterized the arterial pressure, heart rate, and regional vascular conductance responses elicited by unilateral microinjection of ionotropic glutamatergic agonists N-methyl-d-aspartic acid (NMDA and non-NMDA) into the nucleus of tractus solitarius (NTS) of conscious rats. Microinjections of NMDA and S-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) caused changes in mean arterial pressure (MAP). Lower doses elicited decreases in MAP, whereas higher doses elicited biphasic responses (decreases followed by increases). Both agonists induced bradycardia and elicited dose-dependent vasoconstriction in the renal, mesenteric, and hindquarter beds. AMPA elicited delayed vasodilation in the hindquarter bed but NMDA did not. Bradycardia and initial hypotension produced by each agonist were abolished by systemic administration of the muscarinic antagonist methylatropine. However, methylatropine did not affect either the vasoconstriction or the vasodilatation. ...
Peptides, Mar 3, 2018
Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin-an... more Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin-angiotensin system and an initial transitory increase in daily water and NaCl intake. However, the dipsogenic and natriorexigenic responses to angiotensin II (ANG II) have not been tested yet in 2K1C rats. Therefore, in the present study, we evaluated water and 0.3 M NaCl intake induced by water deprivation (WD)-partial rehydration (PR) or intracerebroventricular (icv) ANG II in 2K1C rats. In addition, the cardiovascular changes to these treatments were also evaluated. Male Holtzman rats received a silver clip around the left renal artery to induce 2K1C renovascular hypertension. In the 5th week, a group of animals received a guide cannula in the lateral ventricle for icv injections. Daily water intake increased from the 3rd week after surgery and remained elevated until the 6th week (last recording week), whereas daily 0.3 M NaCl intake transiently increased from the 2nd to the 5th week a...
Neuroscience, 2017
Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake... more Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4th V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4th V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4th V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (a 2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted in the 4th V and bilaterally in the LPBN were used. Aldosterone (250 or 500 ng) into the 4th V combined with vehicle into the LPBN induced no 1.8% NaClintake compared to control (1.5 ± 1.1 and 1.1 ± 0.4, respectively, vs. vehicle into 4th V: 1.0 ± 0.5 ml/2 h). However, aldosterone (250 or 500 ng) into the 4th V combined with moxonidine (0.5 nmol) into the LPBN induced strong ingestion of 1.8% NaCl (12.7 ± 4.6 and 17.6 ± 3.7 ml/2 h, respectively). Aldosterone (250 ng) into the 4th V combined with methysergide (4 lg) into the LPBN also induced 1.8% NaCl intake (17.6 ± 5.4 ml/2 h). These data suggest that the inhibitory mechanisms of the LPBN counteract the facilitation of sodium intake produced by aldosterone injected into the 4th, restraining sodium intake in this condition.
Behavioural brain research, Aug 15, 2017
Angiotensin II (ANG II) is a typical facilitatory stimulus for sodium appetite. Surprisingly, hyp... more Angiotensin II (ANG II) is a typical facilitatory stimulus for sodium appetite. Surprisingly, hyperosmolarity and central cholinergic stimulation, two classical antinatriorexigenic stimuli, also facilitate NaCl intake when they are combined with injections of the α2-adrenoceptor/imidazoline agonist moxonidine into the lateral parabrachial nucleus (LPBN). In the present study, we tested the relative importance of central angiotensinergic and cholinergic mechanisms for the control of water and NaCl intake by combining different dipsogenic or natriorexigenic stimuli with moxonidine injection into the LPBN. Adult male Holtzman rats (n=9-10/group) with stainless steel cannulas implanted in the lateral ventricle and LPBN were used. Bilateral injections of moxonidine (0.5 nmol) into the LPBN increased water and 0.3M NaCl intake in rats that received furosemide+captopril injected subcutaneously, ANG II (50ng) or carbachol (cholinergic agonist, 4 nmol) injected intracerebroventricularly (icv...
Brain Research, 2017
Previously we have demonstrated that microinjection of acetylcholine (ACh) into the intermediate ... more Previously we have demonstrated that microinjection of acetylcholine (ACh) into the intermediate nucleus of the solitary tract (iNTS) induced sympatho-inhibition combined with a decrease in the phrenic nerve activity (PNA), whereas in the commissural NTS (cNTS), ACh did not change sympathetic nerve activity (SNA), but increased the PNA. In view of these demonstrated distinctive effects of ACh in different subnuclei of the NTS the current studies were undertaken to examine, using patch clamp techniques, the specific effects of ACh on the excitability of individual neurons in the NTS, as well as the neuropharmacology of these actions. Coronal slices of the brainstem containing either cNTS or iNTS subnuclei were used, and whole cell patch clamp recordings obtained from individual neurons in these two subnuclei. In cNTS, 58% of recorded neurons (n = 12) demonstrated rapid reversible depolarizations in response to ACh (10 mM), effects which were inhibited by the nicotinic antagonist mecamylamine (10 lM), but unaffected by the muscarinic antagonist atropine (10 lM). Similarly, bath application of ACh depolarized 76% of iNTS neurons (n = 17), although in this case both atropine and mecamylamine reduced the AChinduced depolarization. These data demonstrate that ACh depolarizes cNTS neurons through actions on nicotinic receptors, while depolarizing effects in iNTS are apparently mediated by both receptors.
Behavioural brain research, Jan 17, 2016
Facilitatory and inhibitory mechanisms in the central nucleus of the amygdala (CeA) and the later... more Facilitatory and inhibitory mechanisms in the central nucleus of the amygdala (CeA) and the lateral parabrachial nucleus (LPBN), respectively, are important for the control of sodium and water intake. Here we investigated the importance of the opioid mechanisms in the CeA for water and 0.3M NaCl intake in euhydrated or hyperosmotic rats treated with injections of muscimol (GABAA agonist) or moxonidine (α2 adrenergic/imidazoline agonist) into the LPBN, respectively. Male Holtzman rats (n=4-8/group) with stainless steel cannulas implanted bilaterally in the CeA and in the LPBN were used. The ingestion of 0.3M NaCl and water by euhydrated rats treated with muscimol (0.5nmol/0.2μl) into the LPBN (29.4±2.7 and 15.0±2.4ml/4h, respectively) was abolished by the previous injections of naloxone (opioid antagonist, 40μg/0.2μl) into the CeA (0.7±0.3 and 0.3±0.1ml/4h, respectively). The ingestion of 0.3M NaCl by rats treated with intragastric 2M NaCl (2ml/rat) combined with moxonidine (0.5nmol/...
Brain Research, 2015
The lateral parabrachial nucleus (LPBN) and the central nucleus of the amygdala (CeA) are importa... more The lateral parabrachial nucleus (LPBN) and the central nucleus of the amygdala (CeA) are important central areas for the control of sodium appetite. In the present study, we investigated the importance of the facilitatory mechanisms of the CeA on NaCl and water intake produced by the deactivation of LPBN inhibitory mechanisms. Male Holtzman rats (n ¼7-14) with stainless steel cannulas implanted bilaterally in the CeA and LPBN were used. Bilateral injections of moxonidine (α 2-adrenoceptor/imidazoline agonist, 0.5 nmol/ 0.2 μl) into the LPBN increased furosemideþcaptopril-induced 0.3 M NaCl (29.777.2, vs. vehicle: 4.471.6 ml/2 h) and water intake (26.476.7, vs. vehicle: 8.271.6 ml/2 h). The GABA A agonist muscimol (0.25 nmol/0.2 μl) injected bilaterally into the CeA abolished the effects of moxonidine into the LPBN on 0.3 M NaCl (2.871.6 ml/2 h) and water intake (3.372.3 ml/ 2 h). Euhydrated rats treated with muscimol (0.5 nmol/0.2 μl) into the LPBN also ingested 0.3 M NaCl (19.176.4 ml/4 h) and water (8.873.2 ml/4 h). Muscimol (0.5 nmol/0.2 μl) into the CeA also abolished 0.3 M NaCl (0.170.04 ml/4 h) and water intake (0.170.02 ml/4 h) in euhydrated treated with muscimol into the LPBN. The present results show that neuronal deactivation of the CeA abolishes NaCl intake produced by the blockade of LPBN inhibitory mechanisms, suggesting an interaction between facilitatory mechanisms of the CeA and inhibitory mechanisms of the LPBN in the control of NaCl intake.
American journal of physiology. Heart and circulatory physiology, 2003
N-methyl-d-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptor subtypes are involv... more N-methyl-d-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptor subtypes are involved in the integration of visceral afferent inputs within the nucleus of the solitary tract (NTS). Microinjection studies indicate interactions between nitric oxide (NO) and EAA receptors within the NTS. To examine these interactions at the single cell level, this study characterized the effects of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the NO donor 3-[2-hydroxy-2-nitroso-1-propylhydrazino]-1-propanamine (PAPA-NONOate) on the excitatory responses of vagus nerve (VN)-evoked NTS neurons to the activation of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in rats. Iontophoresis of l-NAME did not alter spontaneous or VN-evoked discharges, but significantly decreased the number of action potentials (APs) evoked by iontophoretic application of AMPA. The effects of l-NAME on NMDA-evoked discharge were variable; for the po...
Acta physiologica (Oxford, England), Jan 10, 2014
Melanocortin receptors (MC3/4R) mediate most of the metabolic and cardiovascular actions of lepti... more Melanocortin receptors (MC3/4R) mediate most of the metabolic and cardiovascular actions of leptin. Here, we tested if MC4R also contributes to leptin's effects on respiratory function. After control measurements, male Holtzman rats received daily microinjections of leptin, SHU9119 (MC3/4R antagonist) or SHU9119 combined with leptin infused into the brain lateral ventricle for 7 days. On the 6th day of treatment, tidal volume (VT ), respiratory frequency (fR ) and pulmonary ventilation (VE ) were measured by whole-body plethysmography during normocapnia or hypercapnia (7% CO2 ). Baseline mean arterial pressure (MAP), heart rate (HR) and metabolic rate were also measured. VE , VT and fR were also measured in mice with leptin receptor deletion in the entire central nervous system (LepR/Nestin-cre) or only in proopiomelanocortin neurones (LepR/POMC-cre) and in MC4R knockout (MC4R(-/-) ) and wild-type mice. Leptin (5 μg day(-1) ) reduced body weight (~17%) and increased ventilatory ...
Arquivos Brasileiros de Ciências da Saúde, 2011
O sódio é o principal íon do líquido extracelular e tem primordial importância para diversas funç... more O sódio é o principal íon do líquido extracelular e tem primordial importância para diversas funções fisiológicas. Manter a concentração plasmática do sódio dentro dos limites fisiológicos é vital para diversas espécies de animais, inclusive os humanos. Portanto, é fundamental que hajam mecanismos responsáveis pela monitorização e manutenção de níveis adequados de sódio no plasma. O apetite ao sódio, o comportamento que comanda a ingestão de sal, é estimulado por situações de deficiência sistêmica de sódio. Ao longo de décadas, diversos estudos foram desenvolvidos a fim de compreender os mecanismos neurais e hormonais envolvidos no controle desse comportamento. No entanto, muitas questões relacionadas a esse assunto ainda permanecem desconhecidas e a cada dia surgem novas evidências. Neste trabalho, foram revistos os fatos históricos, mecanismos neurais, hormonais e os achados mais recentes envolvendo apetite ao sódio.
Arquivos Brasileiros de Ciências da Saúde, 2008
A aldosterona é o mais importante mineralocorticóide circulante. É secretada pela zona glomerulos... more A aldosterona é o mais importante mineralocorticóide circulante. É secretada pela zona glomerulosa da glândula adrenal e atua em orgãos-alvo tais como os rins, cólon, glândulas salivares e sudoríparas por meio de mecanismos genômicos, a fim de manter o equilíbrio hidroeletrolítico do organismo. Mais recentemente vêm surgindo novas descobertas sobre as ações da aldosterona, as quais não se mostram restritas aos alvos clássicos de sua ação. Orgãos como coração, vasos e muitos locais do sistema nervoso central (SNC), são apontados como novos alvos da ação da aldosterona, mostrando efeitos fisiológicos bem como fisiopatológicos, que na maioria das vezes relacionam-se a mecanismos não-genômicos. Os principais efeitos da aldosterona nesses novos alvos incluem: estimulação do apetite ao sódio (Na+), aumento da pressão arterial basal, prejuízo do barorreflexo arterial e produção de hipertrofia e fibrose no tecido cardíaco. Esses novos achados enaltecem o papel da aldosterona como o hormônio...
Neuroscience, 2014
Bilateral injections of the GABA A agonist muscimol into the lateral parabrachial nucleus (LPBN) ... more Bilateral injections of the GABA A agonist muscimol into the lateral parabrachial nucleus (LPBN) induce 0.3 M NaCl and water intake in satiated and normovolemic rats, a response reduced by intracerebroventricular (icv) administration of losartan or atropine (angiotensinergic type 1 (AT 1) and cholinergic muscarinic receptor antagonists, respectively). In the present study, we investigated the effects of the injections of losartan or atropine into the subfornical organ (SFO) on 0.3 M NaCl and water intake induced by injections of muscimol into the LPBN. In addition, using intracellular calcium measurement, we also tested the sensitivity of SFO-cultured cells to angiotensin II (ANG II) and carbachol (cholinergic agonist). In male Holtzman rats with cannulas implanted bilaterally into the LPBN and into the SFO, injections of losartan (1 μg/0.1 μl) or atropine (2 nmol/0.1 μl) into the SFO almost abolished 0.3 M NaCl and water intake induced by muscimol (0.5 nmol/0.2 μl) injected into the LPBN. In about 30% of the cultured cells of the SFO, carbachol and ANG II increased intracellular calcium concentration ([Ca 2+ ] i). Three distinct cell populations were found in the SFO, i.e., cells activated by either ANG II (25%) or carbachol (2.6%) or by both stimuli (2.3%). The results suggest that the activation of angiotensinergic and cholinergic mechanisms in the SFO is important for NaCl and water intake induced by the deactivation of LPBN inhibitory mechanisms with muscimol injections. They also show that there are cells in the SFO activated by both angiotensinergic and cholinergic stimuli, perhaps those involved in the responses to muscimol into the LPBN.
Brazilian Journal of Medical and Biological Research, 1999
Carbon monoxide (CO) is a pollutant commonly recognized for its toxicological attributes, includi... more Carbon monoxide (CO) is a pollutant commonly recognized for its toxicological attributes, including CNS and cardiovascular effects. But CO is also formed endogenously in mammalian tissues. Endogenously formed CO normally arises from heme degradation in a reaction catalyzed by heme oxygenase. While inhibitors of endogenous CO production can raise arterial pressure, heme loading can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests the CNS heme-heme oxygenase-CO system may be independent of the periphery. In the CNS, CO apparently acts in the nucleus tractus solitarii (NTS) promoting changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascular functions in a twofold manner; specifically: 1) heme-derived CO generated within vascular smooth muscle (VSM) can promote vasodilation, but 2) its actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM-and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vascular resistance, and subsequently blood pressure.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2012
Aldosterone acting on the brain stimulates sodium appetite and sympathetic activity by mechanisms... more Aldosterone acting on the brain stimulates sodium appetite and sympathetic activity by mechanisms that are still not completely clear. In the present study, we investigated the effects of chronic infusion of aldosterone and acute injection of the mineralocorticoid receptor (MR) antagonist RU 28318 into the fourth ventricle (4th V) on sodium appetite. Male Wistar rats (280–350 g) with a stainless-steel cannula in either the 4th V or lateral ventricle (LV) were used. Daily intake of 0.3 M NaCl increased to 46 ± 15 and 130 ± 6 ml/24 h after 6 days of infusion of 10 and 100 ng/h of aldosterone into the 4th V (intake with vehicle infusion: 2 ± 1 ml/24 h). Water intake fell slightly and not consistently, and food intake was not affected by aldosterone. Sodium appetite induced by diuretic (furosemide) combined with 24 h of a low-sodium diet fell from 12 ± 1.7 ml/2 h to 5.6 ± 0.8 ml/2 h after injection of the MR antagonist RU 28318 (100 ng/2 μl) into the 4th V. RU 28318 also reduced the int...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2008
Microinjection of acetylcholine chloride (ACh) in the nucleus of the solitary tract (NTS) of awak... more Microinjection of acetylcholine chloride (ACh) in the nucleus of the solitary tract (NTS) of awake rats caused a transient and dose-dependent hypotension and bradycardia. Because it is known that cardiovascular reflexes are affected by nitric oxide (NO) produced in the NTS, we investigated whether these ACh-induced responses depend on NO in the NTS. Responses to ACh (500 pmol in 100 nl) were strongly reduced by ipsilateral microinjection of the NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 10 nmol in 100 nl) in the NTS: mean arterial pressure (MAP) fell by 50 ± 5 mmHg before l-NAME to 9 ± 4 mmHg, 10 min after l-NAME, and HR fell by 100 ± 26 bpm before l-NAME to 20 ± 10 bpm, 10 min after l-NAME (both P < 0.05). Microinjection of the selective inhibitor of neuronal nitric oxide synthase (nNOS), 1-(2-trifluoromethylphenyl) imidazole (TRIM; 13.3 nmol in 100 nl), in the NTS also reduced responses to ACh: MAP fell from 42 ± 3 mmHg before TRIM to 27 ± 6 mmHg, 10 min after TRIM...
American Journal of Physiology-Heart and Circulatory Physiology, 2004
The neuromodulatory effect of NO on glutamatergic transmission has been studied in several brain ... more The neuromodulatory effect of NO on glutamatergic transmission has been studied in several brain areas. Our previous single-cell studies suggested that NO facilitates glutamatergic transmission in the nucleus of the solitary tract (NTS). In this study, we examined the effect of the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME) on glutamatergic and reflex transmission in the NTS. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) from Inactin-anesthetized Sprague-Dawley rats. Bilateral microinjections of l-NAME (10 nmol/100 nl) into the NTS did not cause significant changes in basal MAP, HR, or RSNA. Unilateral microinjection of ( RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 1 pmol/100 nl) into the NTS decreased MAP and RSNA. Fifteen minutes after l-NAME microinjections, AMPA-evoked cardiovascular changes were significantly reduced. N-methyl-d-aspartate (NMDA, 0.5 pmol/100 nl) mic...
Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecti... more Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we demonstrated that the TNF-α receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF-α increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where the majority of pre-sympathetic neurons reside. The activation of these neurons was accompanied by generalized activation of the sympathetic nervous system. Carotid body ablation blunted the TNF-α-induced activation of RVLM-projecting NTS neurons and the increase in splanchnic sympathetic nerve activity. Finally, plasma and spleen levels of cytokines after TNF-α administration were higher in rats subjected to either carotid body ablation or splanchnic sy...
2021 XXXVI Conference on Design of Circuits and Integrated Systems (DCIS), 2021
Deep-Brain Stimulation (DBS) is an emerging area to improve the life of patients with brain decea... more Deep-Brain Stimulation (DBS) is an emerging area to improve the life of patients with brain deceases and one with the most dynamic research towards implantable devices. This paper presents an electronic circuit to generate mild current pulses for application on Deep-Brain Stimulation (DBS). This circuit can generate current pulses with arbitrary shapes in the range of -514µA to +514µA, with a variable frequency up to at least 130Hz, and minimum pulse duration of 90µs. The simulations showed a power consumption of 1.7mW for currents with symmetric shapes and 1.2V. This circuit was designed in a low-power TSMC 65nm CMOS process, targeting implantable devices.
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Papers by Eduardo Colombari