Lesions of the commissural nucleus of the solitary tract reduce arterial pressure in spontaneously hypertensive rats

It has been suggested that increased sympathetic activity and arterial chemoreceptors are important for the high blood pressure in spontaneously hypertensive rats (SHR). Electrolytic lesions of the commissural nucleus of the solitary tract (commNTS) abolish (1) the cardiovascular responses to chemoreflex activation with potassium cyanide (KCN) in normotensive rats and (2) the hypertension that follows acute aortic baroreceptor denervation in rats. Therefore, in this study we investigated the effects of electrolytic lesions of the commNTS on basal mean arterial pressure (MAP), baroreflex, and chemoreflex in SHR and in normotensive control Wistar-Kyoto (WKY) and Wistar rats. CommNTS lesions elicited a dramatic fall in MAP to normal levels during the period of Study (from the first to fourth day following lesions) in SHR and almost no changes in WKY and Wistar rats. The pressor responses to chemoreflex activation with KCN tested in the days 1 and 4 after commNTS lesions were abolished in SHR and in normotensive strains. The reflex tachycardia induced by sodium nitroprusside was also attenuated in days 1 and 4 after commNTS lesions in SHR, WKY, and Wistar rats. The data suggest that the integrity of commNTS is important for the maintenance or high blood pressure in SHR and for the reflex responses dependent on sympathetic activation either in SHR or in normotensive strains.

Antihypertensive responses elicited by central moxonidine in rats: Possible role of nitric oxide

In the present study, we investigated the effects of pretreatment with N-G-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) injected intravenously (IV) on the hypotension, bradycardia, and vasodilation produced by moxonidine (alpha(2)-adrenergic/imidazoline receptor agonist) injected into the fourth brain ventricle (4th V) in rats submitted to acute hypertension that results from baroreflex blockade by bilateral injections of kynurenic acid (kyn, glutamatergic receptor antagonist) into the nucleus of the solitary tract (NTS) or in normotensive rats. Male Wistar rats (n = 5 to 7/group) anesthetized with IV urethane (1.0 g kg(-1) of body weight) and a-chloralose (60mg kg(-1) of body weight) were used. Bilateral injections of kyn (2.7 nmol 100 nL(-1)) into the NTS increased baseline mean arterial pressure (148 +/- 11 mm Hg, vs. control: 102 +/- 4mm Hg) and baseline heart rate (417 +/- 11 bpm, vs. control: 379 +/- 6 bpm). Moxonidine (20 nmol mu L-1) into the 4th V reduced mean arterial pressure and heart rate to similar levels in rats treated with kyn into the NTS (68 +/- 9 mm Hg and 359 +/- 7 bpm) or in control normotensive rats (66 +/- 7 mm Hg and 362 +/- 8 bpm, respectively). The pretreatment with L-NAME (2 5 mu mol kg-1, IV) attenuated the hypotension produced by moxonidine into the 4th V in rats treated with kyn (104 +/- 6 mm Hg) or in normotensive rats (95 +/- 8 mm Hg), without changing bradycardia. Moxonidine into the 4th V also reduced renal, mesenteric, and hindquarter vascular resistances in rats treated or not with kyn into the NTS and the pretreatment with L-NAME IV reduced these effects of moxonidine. Therefore, these data indicate that nitric oxide mechanisms are involved in hypotension and mesenteric, renal, and hindquarter vasodilation induced by central moxonidine in normotensive and in acute hypertensive rats.

AV3V lesions reduce the pressor response to L-glutamate into the RVLM

Neurons from the rostral ventrolateral medulla (RVLM) directly activate sympathetic preganglionic neurons in the spinal cord. Hypertensive responses and sympathetic activation produced by different stimuli are strongly affected by lesions of the preoptic periventricular tissue surrounding the anteroventral third ventricle (AV3V region). Therefore, in the present study, we investigated the effects of acute (1 day) and chronic (IS days) electrolytic lesions of the AV3V region on the pressor responses produced by injections of the excitatory amino acid L-glutamate into the RVLM of unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula. implanted into the RVLM were used. The pressor responses produced by injections of L-glutamate (1, 5 and 10 nmol/100 nl) into the RVLM were reduced 1 day (9 +/- 4, 39 +/- 6 and 37 +/- 4 mm Hg, respectively) and 15 days after AV3V lesions (13 +/- 6, 39 +/- 4 and 43 +/- 4 mm Hg, respectively, vs. sham lesions: 29 +/- 3, 50 +/- 2 and 58 +/- 3 mm Hg, respectively). Injections of L-glutamate into the RVLM in sham or AV3V-lesioned rats produced no significant change in the heart rate (HR). Baroreflex bradycardia and tachycardia produced by iv phenylephrine or sodium nitroprusside, respectively, and the pressor and bradycardic responses to chemoreflex activation with iv potassium cyanide were not modified by AV3V lesions. The results suggest that signals from the AV3V region are important for sympathetic activation induced by L-glutamate into the RVLM. (c) 2006 Elsevier B.V. All rights reserved.

Ablation of NK1 receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats

The nucleus of the solitary tract (NTS) receives primary afferents involved in cardiovascular regulation. We investigated the role of NK1-receptor bearing neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic venous and arterial cannulae. These neurons were lesioned selectively with saporin conjugated with substance P (SP-SAP, 2 mu M, bilateral injections of 20 nL in the subpostremal NTS, or 200 nL in both the subpostremal and the commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we measured changes in blood pressure and heart rate induced by i.v. injection of phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller injections with SP-SAP completely abolished NK1 receptor staining in the subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity in an area that extended from the commissural NTS to the rostral end of the subpostremal NTS. The lesions seemed to affect only a limited number of neurons, since neutral red stained sections did not show any obvious reduction in cell number. The smaller lesions reduced the gain of baroreflex bradycardia and the hypotension induced by phenylbiguanide. The larger lesions completely abolished the response to phenylbiguanide, blocked the baroreflex bradycardia induced by phenylephrine, severely blunted the baroreflex tachycardia, and blocked the bradycardia and reduced the hypertension induced by cyanide. Thus, these responses depend critically on NK1-receptor bearing neurons in the NTS. (c) 2006 Elsevier B.V. All rights reserved.

Angiotensin II-derived reactive oxygen species underpinning the processing of the cardiovascular reflexes in the medulla oblongata

The brainstem is a major site in the central nervous system involved in the processing of the cardiovascular reflexes such as the baroreflex and the peripheral chemoreflex. The nucleus tractus solitarius and the rostral ventrolateral medulla are 2 important brainstem nuclei, and they play pivotal roles in autonomic cardiovascular regulation. Angiotensin II is one of the neurotransmitters involved in the processing of the cardiovascular reflexes within the brainstem. It is well-known that one of the mechanisms by which angiotensin II exerts its effect is via the activation of pathways that generate reactive oxygen species (ROS). In the central nervous system, ROS are reported to be involved in several pathological diseases such as hypertension, heart failure and sleep apnea. However, little is known about the role of ROS in the processing of the cardiovascular reflexes within the brainstem. The present review mainly discussed some recent findings documenting a role for ROS in the processing of the baroreflex and the peripheral chemoreflex in the brainstem.

Inhibition of the caudal pressor area reduces cardiorespiratory chemoreflex responses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Commissural NTS lesions enhance the pressor response to central cholinergic and adrenergic activation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

14-3-3: Defense and regulatory proteins coding by Eucalyptus genome

The data mining of Eucalyptus ESTs genome finds four clusters (EGCEST2257E11.g, EGBGRT3213F11.g, and EGCCFB1223H11.g) from highly conservative 14-3-3 protein family which modulates a wide variety of cellular processes. Multiple alignments were built from twenty four sequences of 14-3-3 proteins searched into the GenBank databases and into the four pools of Eucalyptus genome programs. The alignment has shown two regions highly conservative on the sequences corresponding to the motifs of protein phosphorylation and nine highly conservative regions on the sequence corresponding to the linkage regions of alpha helices structure based on three dimensional of dimer functional structure. The differences of amino acid into the structural and functional domains of 14-3-3 plant protein were identified and can explain the functional diversity of different isoforms. The phylogenic protein trees were built by the maximum parsimony and neighborjoining procedures of Clustal X alignments and PAUP software for phylogenic analysis.

The effect of propolis on CCL5 and IFN-gamma expression by peripheral blood mononuclear cells from leishmaniasis patients

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of thyroid hormone T3 on Myosin-Va expression in the central nervous system

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient - Effects on leptin and insulin signaling pathways

Acting in the hypothalamus, tumor necrosis factor-alpha (TNF-alpha) produces a potent anorexigenic effect. However, the molecular mechanisms involved in this phenomenon are poorly characterized. In this study, we investigate the capacity of TNF-alpha to activate signal transduction in the hypothalamus through elements of the pathways employed by the anorexigenic hormones insulin and leptin. High dose TNF-a promotes a reduction of 25% in 12 h food intake, which is an inhibitory effect that is marginally inferior to that produced by insulin and leptin. In addition, high dose TNF-a increases body temperature and respiratory quotient, effects not reproduced by insulin or leptin. TNF-alpha, predominantly at the high dose, is also capable of activating canonical pro-inflammatory signal transduction in the hypothalamus, inducing JNK, p38, and NF kappa B, which results in the transcription of early responsive genes and expression of proteins of the SOCS family. Also, TNF-a activates signal transduction through JAK-2 and STAT-3, but does not activate signal transduction. through early and intermediary elements of the insulin/leptin signaling pathways such as IRS-2, Akt, ERK and FOXO1. When co-injected with insulin or leptin, TNF-a, at both high and low doses, partially impairs signal transduction through IRS-2, Akt, ERK and FOXO1 but not through JAK-2 and STAT-3. This effect is accompanied by the partial inhibition of the anorexigenic effects of insulin and leptin, when the low, but not the high dose of TNF-alpha is employed. In conclusion, TNF-alpha, on a dose-dependent way, modulates insulin and leptin signaling and action in the hypothalamus. (c) Published by Elsevier B.V.

In vitro and in vivo studies on CCR10 regulation by Annexin A1

The mode of action of annexin A1 (ANXA1) is poorly understood. By using rapid subtraction hybridization we studied the effects of human recombinant ANXA1 and the N-terminal ANXA1 peptide on gene expression in a human larynx cell line. Three genes showed strong downregulation after treatment with ANXA1. In contrast, expression of CCR10, a seven transmembrane G-protein coupled receptor for chemokine CCL27 involved in mucosal immunity, was increased. Moreover the reduction in CCR10 expression induced by ANXA1 gene deletion was rescued by intravenous treatment with low doses of ANXA1. These findings provide new evidence that ANXA1 modulates gene expression. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

OBJECTIVE: ,,,,,Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. ,,,, ,,,, ,,,,,METHODS: ,,,,,Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. ,,,, ,,,, ,,,,,RESULTS: ,,,,,Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05) to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05). ,,,, ,,,, ,,,,,CONCLUSION: ,,,,,Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

Serotonin and circadian rhythms

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of pathogenicity-related genes of Xylella fastidiosa in vitro and in planta

Xylella fastidiosa is responsible for several economically important plant diseases. It is currently assumed that the symptoms are caused by vascular occlusion due to biofilm formation. Microarray technology was previously used to examine the global gene expression profile of X. filstidiosa freshly isolated from symptomatic plants or after several passages by axenic culture medium, and different pathogenicity profiles have been obtained. In the present study the expression of some pathogenicity-related genes was evaluated in vitro and in planta by RT-PCR. The results suggest that adhesion is important at the beginning of biofilm formation, while the genes related to adaptation are essential for the organism's maintenance in planta. Similar results were observed in vitro mainly for the adhesion genes. The pattern of expression observed suggests that adhesion modulates biofilm formation whereas the expression of some adaptation genes may be related to the environment in which the organism is living.