Angiotensin II increases and decreases arterial pressure by acting at angiotensin type 1 and type 2 receptors respectively. Renovascular hypertensive rats exhibit a high level of activity of the peripheral and central renin-angiotensin system. Therefore, in the present study we evaluated the effect of increasing the expression of angiotensin type 2 receptors in the solitary-vagal complex [nucleus of the solitary tract/dorsal motor nucleus of the vagus], a key brainstem region for cardiovascular regulation, on the development of renovascular hypertension. Holtzman normotensive rats were implanted with a silver clip around the left renal artery to induce 2 kidney-1 clip renovascular hypertension. Three weeks later, rats were microinjected in the solitary-vagal complex with either an adeno-associated virus to increase the expression of angiotensin type 2 receptors, or with a control vector. We observed that increasing angiotensin type 2 receptor expression in the solitary-vagal complex attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex and the increase in the low frequency component of systolic blood pressure observed in renovascular hypertensive rats. Further, an observed decrease in mRNA levels of angiotensin converting enzyme 2 in the solitary-vagal complex of renovascular hypertensive rats was restored to control levels following viral-mediated increases in angiotensin type 2 receptors at this site. Collectively, these data demonstrate specific and beneficial effects of angiotensin type 2 receptors via the brain of hypertensive rats, and suggest that central angiotensin type 2 receptors may be a potential target for therapeutics in renovascular hypertension.

The nucleus of the solitary tract (NTS) is the primary site of visceral afferents to the central nervous system. In the present study, we investigated the effects of lesions in the commissural portion of the NTS (commNTS) on the activity of vasopressinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, plasma vasopressin, arterial pressure, water intake, and sodium excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats with 15-20 days of sham or electrolytic lesion (1 mA; 10 s) of the commNTS were used. CommNTS lesions enhanced a 2 M NaCl intragastrically induced increase in the number of vasopressinergic neurons expressing c-Fos in the PVN (28 ± 1, vs. sham: 22 ± 2 c-Fos/AVP cells) and SON (26 ± 4, vs. sham: 11 ± 1 c-Fos/AVP cells), plasma vasopressin levels (21 ± 8, vs. sham: 6.6 ± 1.3 pg/ml), pressor responses (25 ± 7 mmHg, vs. sham: 7 ± 2 mmHg), water intake (17.5 ± 0.8, vs. sham: 11.2 ± 1.8 ml/2 h), and natriuresis (4.9 ± 0.8, vs. sham: 1.4 ± 0.3 meq/1 h). The pretreatment with vasopressin antagonist abolished the pressor response to intragastric 2 M NaCl in commNTS-lesioned rats (8 ± 2.4 mmHg at 10 min), suggesting that this response is dependent on vasopressin secretion. The results suggest that inhibitory mechanisms dependent on commNTS act to limit or counterbalance behavioral, hormonal, cardiovascular, and renal responses to an acute increase in plasma osmolality.

Resumo: a obesidade comumente é associada com outras doenças como: hipertensão arterial, diabetes mellitus tipo II, cardiovasculares e inflamação crônica. Estudos demonstram o tecido adiposo (TA) como um órgão endócrino capaz de influenciar a homeostase energética e hemodinâmica, além de ter papel importante na resposta inflamatória. O termo adipocina é utilizado para nomear peptídeos bioativos sintetizados e secretados por adipócitos. O interesse em estudar essas proteínas teve início com a descoberta da leptina e suas diversas funções, hoje já sabemos que o TA secreta outros hormônios, proteínas de fase aguda, quimiocinas, fatores hemostáticos e hemodinâmicos e fatores de crescimento. Este trabalho teve por objetivo estudar os principais grupos de adipocinas visando uma maior compreensão de seus mecanismos de ação, das finalidades e influências no desenvolvimento da obesidade e estado de inflamação crônica. Foi observado que essas adipocinas em desequilíbrio promovem impacto em diversas funções corporais, alterando a ingesta alimentar, sensibilidade à insulina, resposta imune, angiogênese, pressão arterial, metabolismo lipídico e balanço energético. Dessa maneira se faz necessária uma compreensão dos efeitos do tratamento como atividade física, nutrição, aspecto psicológico e clínica sobre o controle hormonal e de citocinas, a fim de se desenvolver terapias mais eficazes, diminuindo as complicações da obesidade. Palavras-chave: Adipocinas. Leptina. Adiponectina. Resistina. Obesidade.Abstract: the obesity is commonly associated with other diseases such as hypertension, diabetes mellitus type II, cardiovascular and chronic inflammation. Studies revealed adipose tissue (AT) as an endocrine organ capable of influencing the energy and hemodynamic homeostasis, and play an important role in the inflammatory response. The adipokine term is used to name bioactive peptides synthesized and secreted by adipocytes. The interest in studying these proteins began with the discovery of leptin and its various functions, today we know that the TA secret other hormones, acute phase proteins, chemokines, hemostatic and hemodynamic factors and growth factors. This study aims to investigate the major adipokines groups seeking a greater understanding of their mechanisms of action, its purposes and influences the development of obesity and chronic state of inflammation. It was observed that these imbalance adipokines have a impact on several body functions, altering dietary intake, insulin sensitivity, immune response, angiogenesis, blood pressure, lipid metabolism and energy. Thus, a understanding of the effects of treatment such as physical activity, nutrition, psychological and clinical aspects on hormonal and cytokine control is necessary in order to develop more effective therapies, reducing the complications of obesity.

These results indicate that an increased expression of MIF within the nucleus of the solitary tract neurons of SHRs lowers blood pressure and restores baroreflex function.

The aim of this study was to investigate the physiological effects of increased angiotensin II type 2 receptor (AT2R) expression in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus; NTS/DVM) on baroreflex function in non-anaesthetised normotensive (NT) and spontaneously hypertensive rats (SHR). Ten week old NT Holtzman and SHR were microinjected with either an adeno-associated virus expressing AT2R (AAV2-CBA-AT2R) or enhanced green fluorescent protein (control; AAV2-CBA-eGFP) into the NTS/DVM. Baroreflex and telemetry recordings were performed on four experimental groups: 1) NTeGFP, 2) NTAT2R, 3) SHReGFP and 4) SHRAT2R (n=4-7/group). Following in-vivo experimental procedures, brains were harvested for gene expression analysis. Impaired bradycardia in SHReGFP was restored in SHR rats overexpressing AT2R in the NTS/DMV. mRNA levels of angiotensin converting enzyme decreased and angiotensin converting enzyme 2 increased in the NTS/DMV of SHRAT2R compared to SHReGFP. Increased levels of pro-inflammatory cytokine mRNA levels in the SHReGFP group also decreased in the SHRAT2R group. AT2R overexpression did not elicit any significant change in mean arterial pressure (MAP) in all groups from baseline to 4weeks post viral transfection. Both SHReGFP and SHRAT2R showed a significant elevation in MAP compared to the NTeGFP and NTAT2R groups. Increased AT2R expression within the NTS/DMV of SHR was effective at improving baroreflex function but not MAP. We propose possible mediators involved in improving baroreflex are in the ANG II/ACE2 axis, suggesting a potential beneficial modulatory effect of AT2R overexpression in the NTS/DMV of neurogenic hypertensive rats.

The nucleus of the solitary tract (NTS) is the primary site of the cardiovascular afferent information about arterial blood pressure and volume. The NTS projects to areas in the central nervous system involved in cardiovascular regulation and hydroelectrolyte balance, such as the anteroventral third ventricle region and the lateral parabrachial nucleus. The aim of the present study was to investigate the effects of electrolytic lesion of the commissural NTS on water and 0.3 M NaCl intake and the cardiovascular responses to subcutaneous injection of isoproterenol. Male Holtzman rats weighing 280 to 320 g were submitted to sham lesion or electrolytic lesion of the commissural NTS (N = 6-15/group). The sham-lesioned rats had the electrode placed along the same coordinates, except that no current was passed. Water intake induced by subcutaneous isoproterenol (30 µg/kg body weight) significantly increased in chronic (15 days) commissural NTS-lesioned rats (to 2.4 ± 0.2 vs sham: 1.9 ± 0.2 mL 100 g body weight -1 60 min -1 ). Isoproterenol did not induce any sodium intake in sham or in commissural NTS-lesioned rats. The isoproterenol-induced hypotension (sham: -27 ± 4 vs commissural NTS-lesioned rats: -22 ± 4 mmHg/20 min) and tachycardia (sham: 168 ± 10 vs commissural NTS: 144 ± 24 bpm/20 min) were not different between groups. The present results suggest that the commissural NTS is part of an inhibitory neural pathway involved in the control of water intake induced by subcutaneous isoproterenol, and that the overdrinking observed in lesioned rats is not the result of a cardiovascular imbalance in these animals.

No abstract

A previous study has shown that intragastric (ig) 2 M NaCl load increases mean arterial pressure (MAP) in rats with chronic lesions of the commissural nucleus of the solitary tract (commNTS), while in sham rats 2 M NaCl load produces only a slight increase or no change in MAP. In the present study, we investigated the effects of the blockade of vasopressinergic V1 receptors on MAP changes induced by 2 M NaCl ig in commNTS and sham lesioned rats. Male Holtzman rats (280–320 g, n = 8–10/group) with chronic (15 days) sham or electrolytic lesions (1mA, 10 s) of the commNTS were used. Intravenous V1 receptors antagonist (Manning compound, 10 μg/kg b. wt.) or saline were administered 5 minutes before 2 M NaCl ig. MAP was recorded for 60 min after 2 M NaCl load. In commNTS‐ lesioned rats, the pre‐treatment with V1 antagonist blocked the pressor response induced by 2 M NaCl ig (4 ± 4 vs. saline: 24 ± 2 mmHg). Intragastric 2 M NaCl produced no changes in MAP in sham rats pre‐treated with iv saline (7 ± 2 mmHg) or V1 antagonist (−3 ± 2 mmHg). These data suggest that the pressor response induced by intragastric hypertonic saline load in commNTS lesioned depends on vasopressin secretion. Supported by FAPESP