Abstract
The paraventricular nucleus of the hypothalamus (PVN) contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II), which activates AT1 receptors in the circumventricular organs (OCVs), mainly in the subfornical organ (SFO). Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS), leading to increases in sympathetic nerve activity (SNA). Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS): dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin, and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS.
Highlights
The aim of this mini-review is to discuss the role of sympathoexcitation induced by angiotensin II (Ang-II)-dependent reactive oxygen species (ROS) production in the pre-autonomic paraventricular nucleus of the hypothalamus (PVN) neurons in modulating the development and/or metabolic disorders that results in the development and/or the maintenance of metabolic syndrome
The paraventricular nucleus of the hypothalamus is anatomically connected to other hypothalamic areas and to the brainstem, playing a pivotal role in several homeostatic responses, being an important integrative nucleus for autonomic and neuroendocrine functions (Swanson and Sawchenko, 1980; Stern, 2001; Cruz et al, 2008; Cruz and Machado, 2009; Reis et al, 2010)
Our laboratory has been investigating the mechanisms underlying neurogenic hypertension and our results strongly suggest that this pathological condition is caused by Ang-II-dependent ROS accumulation along the subfornical organ (SFO)-PVNRVLM axis (Peterson et al, 2009; Botelho-Ono et al, 2011; Braga et al, 2011; Burmeister et al, 2011; de Queiroz et al, 2013)
Summary
The sympathoexcitation is linked to various diseases; circulating levels of Ang-II modulate SFO angiotensinergic projection to pre-autonomic PVN neurons, which lead to increases in sympathoexcitatory activity to the spinal cord via direct projections (Koshiya and Guyenet, 1996; Badoer, 2001; Stocker et al, 2004) or indirectly projecting to pre-sympathetic neurons in the RVLM (Koshiya and Guyenet, 1996; Badoer, 2001; Ito et al, 2002; Stocker et al, 2004). Increasing evidence supports the premise that Ang-II in the PVN is involved in pathological conditions originating from sympathoexcitation, such as hypertension, heart failure, diabetes, obesity, and metabolic syndrome (Gutkind et al, 1988; Ito et al, 2002; Oliveira-Sales et al, 2009; Braga et al, 2011). It has been demonstrated that Ang-II increase reactive oxygen species (ROS) along the subfornical organ–paraventricular nucleus of the hypothalamus–rostral ventrolateral medulla axis [SFO-PVN-RVLM axis (Oliveira-Sales et al, 2008; Braga et al, 2011; Burmeister et al, 2011)]
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