O bloqueio do sistema renina-angiotensina atenua a remodelação cardíaca de ratos submetidos a estenose aórtica

OBJETIVO: Avaliar o papel do bloqueador dos receptores AT1 e do inibidor da enzima conversora da angiotensina na remodelação cardíaca induzida por estenose aórtica em ratos. MÉTODOS: Ratos Wistar foram divididos em 4 grupos: controle (C, n=13), estenose aórtica (EAo, n=11), EAo com lisinopril, 20 mg/kg/dia (LIS, n=11) e EAo com losartan, 40 mg/kg/dia (LOS, n=9). Os tratamentos foram iniciados 3 dias antes da cirurgia. Após 6 semanas, os animais foram submetidos ao estudo ecocardiográfico, quantificação da concentração de hidroxiprolina e da área seccional (CSA) miocitária do ventrículo esquerdo (VE). RESULTADOS: A EAo induziu aumento da espessura da parede do VE. Os animais LIS e LOS não apresentaram diferença em relação aos animais controles. Os ratos EAo e LIS apresentaram maiores diâmetros do átrio esquerdo que os ratos controles, enquanto nos animais LOS não houve diferença. Os animais com EAo apresentaram maiores valores da porcentagem de encurtamento que os controle. Esse fato não foi modificado com LIS ou LOS. A CSA dos animais do grupo EAo foi maior que a dos controle. Entretanto, o tratamento com LOS e com LIS atenuou o aumento da área induzida pela EAo. A EAo resultou em aumento na concentração de HOP, enquanto o grupo LOS não apresentou diferença em relação ao grupo controle. CONCLUSÃO: O bloqueio do sistema renina-angiotensina, com bloqueador AT1 e com IECA, pode atenuar o desenvolvimento de hipertrofia cardíaca, porém só o bloqueio dos receptores AT1 atenua a fibrose intersticial do VE.

Uso de medicamentos por pessoas com deficiências em áreas do estado de São Paulo

OBJETIVO: Analisar o consumo de medicamentos e os principais grupos terapêuticos consumidos por pessoas com deficiências físicas, auditivas ou visuais. MÉTODOS: Estudo transversal em que foram analisados dados do Inquérito Multicêntrico de Saúde no Estado de São Paulo (ISA-SP) em 2002 e do Inquérito de Saúde no Município de São Paulo (ISA-Capital), realizado em 2003. Os entrevistados que referiram deficiências foram estudados segundo as variáveis que compõem o banco de dados: área, sexo, renda, faixa etária, raça, consumo de medicamentos e tipos de medicamentos consumidos. RESULTADOS: A percentagem de consumo entre as pessoas com deficiência foi de: 62,8% entre os visuais; 60,2% entre os auditivos e 70,1% entre os físicos. As pessoas com deficiência física consumiram 20% mais medicamentos que os não-deficientes. Entre as pessoas com deficiência visual, os medicamentos mais consumidos foram os diuréticos, agentes do sistema renina-angiotensina e analgésicos. Pessoas com deficiência auditiva utilizaram mais analgésicos e agentes do sistema renina-angiotensina. Entre indivíduos com deficiência física, analgésicos, antitrombóticos e agentes do sistema renina-angiotensina foram os medicamentos mais consumidos. CONCLUSÕES: Houve maior consumo de medicamentos entre as pessoas com deficiências quando comparados com os não-deficientes, sendo os indivíduos com deficiência física os que mais consumiram fármacos, seguidos de deficientes visuais e auditivos.

Maternal undernutrition and the offspring kidney: from fetal to adult life

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

Serotonergic mechanisms of the lateral parabrachial nucleus and cholinergic-induced sodium appetite

Central cholinergic mechanisms are suggested to participate in osmoreceptor-induced water intake. Therefore, central injections of the cholinergic agonist carbachol usually produce water intake (i.e., thirst) and are ineffective in inducing the intake of hypertonic saline solutions (i.e., the operational definition of sodium appetite). Recent studies have indicated that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nucleus (LPBN) markedly increases salt intake in models involving the activation of the renin-angiotensin system or mineralocorticoid hormones. The present studies investigated whether sodium appetite could be induced by central cholinergic activation with carbachol (an experimental condition where only water is typically ingested) after the blockade of LPBN serotonergic mechanisms with methysergide treatment in rats. When administered intracerebroventricularly in combination with injections of vehicle into both LPBN, carbachol (4 nmol) caused water drinking but insignificant intake of hypertonic saline. In contrast, after bilateral LPBN injections of methysergide (4 mug), intracerebroventricular carbachol induced the intake of 0.3 M NaCl. Water intake stimulated by intracerebroventricular carbachol was not changed by LPBN methysergide injections. The results indicate that central cholinergic activation can induce marked intake of hypertonic NaCl if the inhibitory serotonergic mechanisms of the LPBN are attenuated.

Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

Previous studies have indicated the importance of angiotensin II (ANG II) in skeletal muscle angiogenesis. The present study explored the effect of regulation of the renin gene on angiogenesis induced by electrical stimulation with the use of physiological, pharmacological, and genetic manipulations of the renin-angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred substrain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. This restored response was significantly attenuated when SS-13BN/Mcwi consomic rats were treated with lisinopril or high-salt diet. The role of ANG II on this effect was confirmed by the complete restoration of skeletal muscle angiogenesis in SS/Mcwi rats infused with subpressor doses of ANG II. Congenic strains derived from the SS-13BN/Mcwi consomic were used to further verify the role of the renin gene in this response. Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below (congenic line B) the renin gene. The present study emphasizes the importance of maintaining normal renin regulation as well as ANG II levels during the angiogenesis process with a combination of physiological, genetic, and pharmacological manipulation of the RAS.

Multifactorial control of water and saline intake: Role of α2-adrenoceptors

Water and saline intake is controlled by several mechanisms activated during dehydration. Some mechanisms, such as the production of angiotensin II and unloading of cardiovascular receptors, activate both behaviors, while others, such as the increase in blood osmolality or sodium concentration, activate water, but inhibit saline intake. Aldosterone probably activates only saline intake. Clonidine, anα2-adrenergic agonist, inhibits water and saline intake induced by these mechanisms. One model to describe the interactions between these multiple mechanisms is a wire-block diagram, where the brain circuit that controls each intake is represented by a summing point of its respective inhibiting and activating factors. The α2-adrenoceptors constitute an inhibitory factor common to both summing points.

Remodelação cardíaca induzida pelo tabagismo (tabaquismo)

Previous studies accomplished by our group suggest that tobacco smoke exposure results in cardiac remodeling, with progressive ventricular dysfunction. However, the mechanisms involved in this process are not known. Therefore, our laboratory has been trying to identify the potentials responsible mechanisms for cardiac remodeling induced by tobacco. The blood pressure increase, the renin-angiotensin system and the oxidative stress can modulate this process. On the other hand, the activation of MMP-2 or MMP-9, as well as lipid peroxidation, don't seem to participate of the morphologic and functional alterations induced by tobacco smoke exposure.

Papel das vias angiotensinérgicas no ventrículo cardíaco esquerdo de ratos submetidos à restrição proteica ou desnutrição gestacional

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito do bloqueio da aldosterona na remodelação cardíaca de ratos espontaneamente hipertensos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da glibenclamida na função e histologia renais, em ratos submetidos à hemorragia aguda sob anestesia com sevoflurano

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da revascularização renal sobre a evolução da disfunção renal na nefropatia isquêmica aterosclerótica

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

Understanding the influence of oxidative stress and physical exercise in the relationship between blood pressure and uric acid

Due to the high incidence and prevalence of hypertension, especially in the elderly population, several studies have been developed to understand the relationship between etiological factors and blood pressure control. It has been demonstrated that hypertensive patients tend to present a status of hyperuricemia. This result suggested that there is a relationship between blood pressure and uric acid concentrations. However there is still a lack of studies that focus on this relationship, and especially how physical exercise could affect the relationship between both of them. Thus, the purpose of this study is to review and discuss the relationship between hypertension and uric acid concentration pointing the oxidative stress as the main factor of this relationship and discuss the physical exercise as the main preventive factor of high uric acid concentrations and oxidative stress. It has been described an increase in oxidative stress during the uric acid pathway because the high production of anions superoxide. This in turn, increases the activation of renin-angiotensin system and decreases nitric oxide bioavailability which will compromise the vasodilatation mechanism. However physical exercises have been associated with improvements in antioxidant capacity and nitric oxide production and bioavailability which will improve the blood pressure control.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

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

Endothelial and neuronal nitric oxide synthase inhibitors influences angiotensin II pressor effect in central nervous system

The present study investigated the central role of angiotensin II and nitric oxide on arterial blood pressure (MAP) in rats. Losartan and PD123349 AT 1 and AT 2 (selective no peptides antagonists angiotensin receptors), as well as FK 409 (a nitric oxide donor), N W-nitro-L-arginine methyl ester (L-NAME) a constituve nitric oxide synthase inhibitor endothelial (eNOSI) and 7-nitroindazol (7NI) a specific neuronal nitric oxide synthase inhibitor (nNOSI) were used. Holtzman strain, (Rattus norvergicus) weighting 200-250 g were anesthetized with zoletil 50 mg kg -1 (tiletamine chloridrate 125 mg and zolazepan chloridrate 125 mg) into quadriceps muscle anda stainless steel cannula was stereotaxically implanted into their Lateral Ventricle (LV). Controls were injected with a 0.5 μl volume of 0.15 M NaCl. Angiotensin II injected into LV increased MAP (19±3 vs. control 3±1 mm Hg), which is potentiated by prior injection of L-NAME in the same site 26±2 mm Hg. 7NI injected prior to ANG II into LV also potentiated the pressor effect of ANG II but with a higher intensity than L-NAME 32±3 mm Hg. FK 409 inhibited the pressor effect of ANG II (6±1 mm Hg). Losartan injected into LV before ANG II influences the pressor effect of ANG II (8±1 mm Hg). The PD 123319 decreased the pressor effects of ANG II (16±1 mm Hg). Losartan injected simultaneously with FK 409 blocked the pressor effect of ANG II (3±1 mm Hg). L-NAME produced an increase in the pressor effect of ANG II, may be due to local vasoconstriction and all at once by neuronal NOS inhibition but the main effect is of the 7-NIT an specific nNOS inhibitor. The AT 1 antagonist receptors improve basal nitric oxide (NO) production and release. These data suggest the involvement of constitutive and neuronal NOS in the control of arterial blood pressure induced by ANG II centrally, evolving AT 1 receptor-mediated vasoconstriction and AT 2 receptor-mediated vasodilatation. These results were confirmed by the experiment using FK 409. © 2006 Asian Network for Scientific Information.

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.