Nitrergic neurotransmission in the paraventricular nucleus of the hypothalamus modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats.

We investigated the involvement of nitrergic neurotransmission within the paraventricular nucleus of the hypothalamus (PVN) in modulation of local neuronal activation, autonomic and neuroendocrine responses and behavioral consequences of acute restraint stress in rats. Bilateral microinjections of the selective neuronal nitric oxide (NO) synthase (nNOS) inhibitor Nw-Propyl-L-arginine (NPLA) or the NO scavenger carboxy-PTIO into the PVN reduced arterial pressure and heart rate increases, as well as the fall in cutaneous tail temperature induced by restraint stress. PVN injection of either NPLA or carboxy-PTIO also inhibited restraint-induced increases in anxiety-related behaviors in the elevated plus-maze 24 h later. Local microinjection of NPLA or carboxy-PTIO into the PVN reduced the number of c-fos-immunoreactive neurons in the dorsal parvocellular, ventromedial, medial parvocellular and lateral magnocelllular portions of the PVN in animals subjected to restraint stress. However, neither NPLA nor carboxy-PTIO into the PVN affected restraint-induced increases in plasma corticosterone concentration. The present results indicate that PVN nitrergic neurotransmission acting via nNOS activation has a facilitatory influence on autonomic responses to acute restraint and the delayed emotional consequences of restraint stress. Our results also provide evidence of a prominent role of local nitrergic neurotransmission in PVN neuronal activation during stress.

Vasoprotective effects of neurocompensatory response to balloon injury during diabetes involve the improvement of Mas signaling by TGFß1 activation.

Balloon injury in diabetic rats triggers a sensory neurocompensatory response that restores the blood flow in contralateral carotid. These vasoprotective effects result from H2O2-mediated relaxation that counteracts AT1-dependent contractile hyperreactivity. The most important mechanism from the renin-angiotensin-system in counteracting AT1-mediated effects is that one is mediated by Mas receptors. Thus, we hypothesized that the vasoprotective effects of balloon neurocompensation in diabetic rats could result from the improvement of Mas signaling by H2O2-mediated sensory mechanisms. NK1 receptors are sensory components whose activation could lead to H2O2 generation upon TGFß1 release and ALK5-mediated Nox4 upregulation. Based on this, we aimed to investigate: (1) the role of the TGFß1/ALK5-Nox4-H2O2 pathway on modulating Mas signaling in diabetic rat contralateral carotid; and (2) the contribution of Mas signaling in the control of local blood flow. Our results showed that balloon neurocompensation restored diabetic rat contralateral carotid flow by improving Mas signaling through NK1-mediated TGFß1 release. TGFß1/ALK5 activation enhanced Nox4 expression and Nox4-driven generation of H2O2. In turn, H2O2 enhanced the local Mas-mediated relaxation. Since restenosis impairs diabetic rat ipsilateral carotid flow, the restoration of diabetic rat contralateral carotid flow may prevent further damages in cerebral irrigation by carotid pathways after angioplasty during diabetes.

Cardiovascular responses to ATP microinjected into the paraventricular nucleus are mediated by nitric oxide and NMDA glutamate receptors in awake rats.

We hypothesize that a local ATP-NO-NMDA glutamate receptor interaction in the paraventricular nucleus (PVN) modulates the baseline mean arterial pressure and heart rate in unanaesthetized rats. The microinjection of α,ß-methylene ATP [methyl ATP; 0.06, 0.12 and 1.2 nmol (100 nl)(-1)] into the PVN caused pressor and tachycardiac responses. Cardiovascular responses evoked by methyl ATP [0.12 nmol (100 nl)(-1)] in the PVN were blocked by pretreatment with the ganglion blocker pentolinium (5 mg kg(-1) i.v.). Also, responses to the injection of methyl ATP [0.12 nmol (100 nl)(-1)] into the PVN were reduced by pretreatment with the selective P2 purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid [0.5 nmol (100 nl)(-1)], the neuronal NO synthase inhibitor N(ω)-propyl-l-arginine [0.04 nmol (100 nl)(-1)] or the selective NMDA glutamate receptor antagonist LY235959 [2 nmol (100 nl)(-1)]. In addition, an injection of the NO donor sodium nitroprusside [27 nmol (100 nl)(-1)] into the PVN caused similar cardiovascular responses to those observed after methyl ATP, which were blocked by local pretreatment with LY235959. Therefore, the present results suggest that cardiovascular responses evoked by methyl ATP in the PVN involve a local production of NO, which promotes local glutamate release and activation of NMDA receptors that are probably located in pre-autonomic parvocellular neurons, leading to sympathetic nervous system stimulation.

Cannabidiol inhibits the hyperphagia induced by cannabinoid-1 or serotonin-1A receptor agonists.

Δ9-THC is a component of Cannabis sativa that increases food intake in animals and humans, an effect prevented by selective CB1 receptor antagonists. Cannabidiol (CBD) is another constituent of this plant that promotes several opposite neuropharmacological effects compared to Δ9-THC. CBD mechanisms of action are still not clear, but under specific experimental conditions it can antagonize the effects of cannabinoid agonists, block the reuptake of anandamide and act as an agonist of 5-HT1A receptors. Since both the cannabinoid and serotoninergic systems have been implicated in food intake control, the aim of the present work was to investigate the effects caused by CBD on hyperphagia induced by agonists of CB1 or 5-HT1A receptors. Fed or fasted Wistar rats received intraperitoneal (i.p.) injections of CBD (1, 10 and 20 mg/kg) and food intake was measured 30 min later for 1 h. Moreover, additional fed or fasted groups received, after pretreatment with CBD (20 mg/kg) or vehicle, i.p. administration of vehicle, a CB1 receptor agonist WIN55,212-2 (2 mg/kg) or a 5-HT1A receptor agonist 8-OH-DPAT (1 mg/kg) and were submitted to the food intake test for 1 h. CBD by itself did not change food intake in fed or fasted rats. However, it prevented the hyperphagic effects induced by WIN55,212-2 or 8-OH-DPAT. These results show that CBD can interfere with food intake changes induced by a CB1 or 5-HT1A receptor agonist, suggesting that its role as a possible food intake regulator should be further investigate.

Acetylcholine-induced aortic relaxation studied in salbutamol treated rats.

It has been proposed that the acetylcholine (ACh)-induced relaxation of the rat aorta is entirely mediated by endothelium derived-nitric oxide (NO). However, some authors have reported that indomethacin pretreatment attenuates ACh-induced relaxation of rat aortic ring preparations. Moreover, it has also been suggested that cAMP accumulation may regulate either nitric oxide synthase (NOS) or cyclooxygenase (COX) expression in different tissues. Thus, in this in vitro study we have investigated the endothelial mechanisms involved in the ACh-induced relaxation of ring preparations of the rat thoracic aorta, as well as the influence chronic treatment with the selective beta(2)-agonist salbutamol had upon such mechanisms. Results of functional experiments show that N(G)-monomethyl-L-arginine (L-NMMA, 3 x 10(-4) M) considerably inhibited the ACh-induced relaxation of rat aortic ring preparations. However, indomethacin (10(-5) M) was also found to partially attenuate this ACh response, suggesting that although NO is the most important mediator of the ACh-induced relaxation of the rat aortic ring preparations, vasorelaxation may also involve prostanoids. Moreover, the results suggest that treatment with salbutamol failed to produce any change in the ACh-induced relaxation of rat aortic ring preparations.

Effect of antihypertensive agents on stellate cells during liver regeneration in rats

BACKGROUND: Although most studies have focused on the hepatocytes, all the hepatic cells participate in the regenerative process, among them the stellate cells. The stellate cells are mesenchymal cells involved in local neurotransmission and paracrine regulation of several liver functions. Acute hepatic tissue loss promotes the proliferation and activation of stellate cells from a quiescent state to myofibroblast-like cells. AIM: Investigate the effects of antihypertensive agents on the stellate cell population during the liver regenerative phenomenon in rats. METHODS: Adult male Wistar rats received lisinopril, losartan, bradykinin, or saline solution in a proportional volume, intraperitoneally, before and after 70 percent partial hepatectomy. Animals from the experimental and saline groups were sacrificed at 36 hours after partial hepatectomy. The alpha-smooth muscle actin labelled stellate cells population was counted in the periportal and pericentral zones of the liver specimen. RESULTS: The labelled stellate cells were more numerous in the control group both in the periportal and pericentral zones at 36 hours after partial hepatectomy than at the other times. The population of stellate cells was significantly lower in the losartan group and higher in the bradykinin and lisinopril groups than in the control group. CONCLUSIONS: These results suggest that losartan can inhibit and bradykinin and lisinopril can stimulate the stellate cell population during liver regeneration in rats. These cells synthesize several substances to stimulate liver regeneration.

Effect of angiotensin-converting enzyme inhibitors on liver regeneration in rats.

BACKGROUND/AIMS: We previously reported that bradykinin augments liver regeneration in rats. The angiotensin-converting enzyme is also a powerful bradykinin-degrading enzyme. METHODOLOGY: Adult rats received lisinopril, captopril, enalaprilat, or saline solution, intraperitoneally, for 5 days before 70% partial hepatectomy, and daily after surgery. They received also losartan and bradykinin. Rats were sacrificed at 12, 24, 36, 48, 72, and 120 hours after hepatectomy. Liver regeneration was evaluated in terms of the restoration of liver weight in proportion to body weight, liver DNA content and immunostaining for proliferating cell nuclear antigen. RESULTS: The proliferating cell nuclear antigen labeling index was higher in the lisinopril-treated group than in the control group at all time points after hepatectomy, except 120 hours. The remnant liver dry weight was higher in lisinopril-treated rats than in control rats at early time points after surgery. The liver DNA content was higher in three angiotensin-converting enzyme inhibitor-treated groups than in the control group at 36 hours after hepatectomy. The bradykinin-induced regenerative response was similar to the lisinopril-induced response, and losartan induced a lower hepatocyte labeling index in comparison to the control group at 36 hours after hepatectomy. CONCLUSIONS: The present results provide evidence that angiotensin-converting enzyme inhibitors remarkably enhance liver regeneration.

Efeito de agentes anti-hipertensivos sobre as células estreladas durante a regeneraçäo hepática em ratos / Effect of antihypertensive agents on the starry cells during hepatic regeneration in rats

O efeito de um inibidor da enzima conversora da angiotensina (lisinopril), de um antagonista do receptor da angiotensina II (losartan) e da bradicinina na população de células estreladas (CE) durante o fenômeno regenerativo hepático foi estudado. Ratos machos Wistar receberam lisinopril, losartan, bradicinina ou solução salina em volumes proporcionais, intraperitonealmente, antes e após hepatectomia parcial a 70 por cento (HP). Cinco animais de cada grupo experimental e controle foram sacrificados sob anestesia com éter em 36 horas após a HP. A população de CE marcadas para alfa-actina de músculo liso foi estimada nas zonas periportal e pericentral das amostras hepáticas. A população de CE foi menor no grupo tratado com losartan, e maior nos grupos tratados com bradicinina e lisinopril que no grupo controle. Estes resultados sugerem que o losartan pode inibir, e a bradicinina e o lisinopril podem estimular a população de CE durante a regeneração hepática em ratos.

Cerebral ventricle sites involved in the central hypertensive response to acetylcholine in unanesthetized rats

It is well known that the injection of acetylcholine (ACh) into the lateral ventricles of the brain (ICV) causes blood pressure increases in unanesthetized rats. However, the actual brain nuclei involved in the mediation of the pressor response to ACh are yet unknown. We report doserelated pressor responses when ACh was injected into the III ventricle or the cerebral aqueduct of similar magnitude to those observed after ICV injection of ACh. No blood pressure effects were observed after the injection of ACh into the IV ventricle. Obstructions of selected ventricular spaces with plugs of Nivea cream were performed to identify the ventricular area involved in the pressor response to ICV-injected ACh. Obstructions of the III ventricle or the aqueduct were similarly effective in significantly reducing the pressor response to ACh injected into the lateral ventricle. Obstructions of the IV ventricle did not affect the pressor response to ICV-injected ACh. The results with the injection of ACh into different ventricular spaces and the occlusion of delimited portions of the ventricular spaces suggest: 1) That prosencephalic, diencephalic as well as rhombencephalic nuclei play a minor role in the mediation of the pressor response to ICV-injected ACh, and 2) that the major site involved in the pressor response to ACh is located in a brain area close to the cerebral aqueduct.

Epidemiology of Chagas' heart disease

Chagas' disease is a major public health problem in Latin America. About 16 million persons are affected and 90 million others are exposed to the risk of being infected by the parasite. The knowledge of epidemiological aspects of the disease allowed to delineate the strategies for the control of the disease related with the vectorial transmission. However, these strategies have had no priority in all endemic countries. Rural-urban migration in most endemic areas carried infected individuals to urban centers increasing the problem of Chagas' disease by blood transfusion. In Brazil the control program has reached good results in the last years and in several states the vectorial transmission was controlled. More recently, hemotherapic practices are performed using screening procedures but this practice must be improved in order to eliminate the possibility of Chagas' disease transmission by another ways (congenital, accidental, oral, etc.). An adequate health care to the infected persons must be improved in order to diminish the social costs of the severe cardiopathy which has been responsible for the adults premature deaths.

Parasitismo natural de bufalinos em Botucatu, SP, Brasil: III. Dinâmica do parasitismo gastro-intestinal em vacas e suas crias / Natural parasitsm of buffalo cows in Botucatu, SP, Brazil: III. Dynamics of gastro-intestinal parasitism in cows and calves

Natural parasitism of buffalo cows in Botucatu, SP, Brazil - III. Dynamics of gastro-intestinal parasitism in cows and calves - Gastro-intestinal parasitism of 24 buffalo cows before parturition, and post-parturition, their infection and that of their respective calves during the following 30 weeks were studied. Willis, Hoffmann and whenever possible, the modified Gordon & Whitlock techniques were used for fecal examinations. Toxocara vitulorum eggs were the earliest forms encountered in calves feces, as follows: during the 1st week after birth, 58.33% of the calves were positive, and in the 4th week, 100% of these animals were positive. Eggs of Strongyloides sp were in the 1st week after birth in two of the calves and in the 5th week, all for them were positive. The next parasites to appear were the Coccidia of which oocysts were detected in the feces of two calves in the 2nd week after birth, and 58.33% of the calves were positive for these in the 3rd week, and in the 6th week, all calves shed oocysts in their feces. On the other hand, eggs of Strongylids were the last forms to appear in calves feces. However, despite their sporadic appearance in the feces, eggs of these parasites were observed continuously from the 11th week onwards, and at this point, the percentage of positive samples began to increase to reach its peak. Relatively to adult animals, eggs of T. vitulorum were observed in the feces of 11 cows, one or twice at most; eggs of Strongyloides sp were seen only once in the feces of four buffalo cows and eggs of Strongylids in 21 out of 24 cows. Oocysts of Coccidia were observed in 16 cows. Mechanisms of infestation of calves with these parasites are discussed

Chromosomes of Pomacea sp (Perry, 1811) (Mesogastropoda, Mollusca)

O estudo cariótípico em Pomacea sp é importante em virtude das grandes dificuldades taxonômicas apresentadas por este gênero e também por ser utilizado em experiências como controlador biológico da Biomphalaria glabrata, hospedeiro intermediário do Schistosoma mansoni. A técnica utilizada para a obtençäo de metáfase foi a de suspensäo celular, elabroada em nosso laboratório. O cariótipo foi obtido em preparaçöes realizadas com embriöes, no estágio de veliger jovem. Esta espécie possui o numero diplóide de 2n=28 cromossomos constituído de 9 pares metacêntricos, 4 pares submetacêntricos e 1 par subtelocêntrico. O braço curto do par subtelocêntrico se mostrou positivo ao AgNO3, local da constriçäo secundária (RON). A análise meiótica confirmou a presença de n=14 cromossomos

CNS catecholaminergic mechanisms in cardiovascular control

Existem evidências conclusivas da participaçäo de catecolaminas na mediaçäo central da pressäo arterial. A atuaçäo das catecolaminas estende-se a todos os segmentos do controle cardiovascular pelo SNC, envolvendo tanto a ativaçäo dos sistemas nervosos simpático e hipotalâmicos-neurohipofisário quanto modulaçäo da atividade vagal parassimpática. A seletividade dessa atuaçäo difusa é garantida pela multiplicidade de receptores envolvidos, possibilitando atuaçäo tanto inibitória quanto excitatória das catecolaminas em um mesmo neurônio. A ativaçäo desses receptores pode causar tanto elevaçäo da pressäo arterial como respostas hipotensoras, dependendo da espécie animal estudada, do sitio de administraçäo ou da utilizaçäo ou näo de anestésicos. Entretanto, existem evidências indicativas de que mecanismos alfa2-centrais estariam preferencialmente envolvidos na mediaçäo de respostas hipotensoras, enquanto mecanismos alfa1-atuariam mediando respostas hipertensoras. Por outro lado, o papel desempenhado por receptores ß-adrenérgicos centrais é ainda controvertido, envolvendo sua participaçäo tanto em respostas pressoras quanto depressoras

Parasitismo natural de bufalinos em Botucatu, S.P., Brasil. I. Observaçöes sobre Toxocara vitulorum Goeze, 1782 / Natural parasitism of the buffalo en Botucatu, S.P., Brazil. I. Observations on Toxocara vitulorum Goeze, 1782

Durante a gestaçäo e depois do parto, amostras de fezes de 24 vacas búfalas e de suas respectivas crias foram examinadas usando-se os métodos de WILLIS, HOFFMAN e, quando possível, GORDON & WHITLOCK. Em 45,83% das búfalas foram observados, por uma ou no máximo duas vezes, ovos do parasita nas fezes, em duas delas 30 dias antes do parto e em oito cerca de 30 dias após, o que leva a supor que mecanismos hormonais relacionados ao parto ou lactaçäo tenham açäo sobre a relaçäo parasita-hospedeiro. Dos bezerros 100% mostraram-se parasitados, 58,33% deles na primeira semana de vida, 87,50% na segunda, 95,83% na terceira e 100% deles na quarta. O encontro inicial de ovos nas fezes dos bezerros indica que a maioria deles infestou-se por via transplacentária, havendo apenas alguns que talvez tenham se infestado via leite. A partir da 18a. semana de vida näo foram detectados ovos nas fezes (no máximo até 118 dias), sendo que a duraçäo do período de positividade variou de três a 17 semanas. Näo foram constatadas diferenças entre bezerros machos e fêmeas quanto ao parasitismo por T. vitulorum, nem correlaçäo entre o número de vezes que as vacas gestaram e a infestaçäo dos bezerros delas nascidos

Cryptosporidiosis among patients with acquired immunodeficiency syndrome (AIDS) in the county of Säo Paulo, Brazil

Criptosporidiose em pacientes acometidos pela síndrome de imunodeficiência adquirida (AIDS), no município de Säo Paulo, Brasil. Amostras de fezes de 157 pacientes acometidos pela síndrome de imunodeficiência adquirida, residentes no município de Säo Paulo, foram submetidas a diversas técnicas para pesquisa de Cryptosporidium sp... Entre as diversas técnicas testadas para o preparo das lâminas (esfregaço direto, método de sedimentaçäo espontânea e concentraçäo pelo formol-éter) a concentraçäo pelo formol-éter foi a que forneceu melhores resultados, superando nitidamente as demais. Nas 157 amostras preparadas por esta técnica, após coloraçäo pelo método de Kinyoun ou pela fucsinacarbólica dimetilsulfóxido, encontraram-se 19 (12,1%) positivas para oocistos de Cryptosporidium sp.