Maternal high-fat diet changes breathing pattern and causes excessive sympathetic discharge in juvenile offspring rat.

Early life over-nutrition, as experienced in maternal obesity, is a risk factor for developing cardiorespiratory and metabolic diseases. Here we investigated the effects of high-fat diet (HFD) consumption on the breathing pattern and sympathetic discharge to blood vessels in juvenile offspring from dams fed with HFD (O-HFD). Adult female Holtzman rats were given a standard diet (SD) or HFD from 6 wk before gestation to weaning.

Acute inhibition of nicotinamide adenine dinucleotide phosphate oxidase in the commissural nucleus of the solitary tract reduces arterial pressure and renal sympathetic nerve activity in renovascular hypertension.

Background: A growing body of evidence suggests that oxidative stress plays a role in the pathophysiology of hypertension. However, the involvement of the reactive oxygen species (ROS) in the commissural nucleus of the solitary tract (commNTS) in development the of hypertension remains unclear.

Method: We evaluated the hemodynamic and sympathetic responses to acute inhibition of NADPH oxidase in the commNTS in renovascular hypertensive rats.

Sympathetic and angiotensinergic activity in spontaneously hypertensive rats treated with 3-amino-1,2,4-triazole.

Previous studies from our laboratory have shown that the pressor response to intracerebroventricular (icv) administered ANG II in normotensive rats or spontaneously hypertensive rats (SHRs) is attenuated by increased central HO concentration, produced either by direct HO icv injection or by increased endogenous HO centrally in response to local catalase inhibition with 3-amino-1,2,4-triazole (ATZ). In the present study, we evaluated the effects of ATZ administered peripherally on arterial pressure and sympathetic and angiotensinergic activity in SHRs. Male SHRs weighing 280-330 g were used.

Chronic administration of catalase inhibitor attenuates hypertension in renovascular hypertensive rats.

Aims: Reactive oxygen species like hydrogen peroxide (HO) are produced endogenously and may participate in intra- and extracellular signaling, including modulation of angiotensin II responses. In the present study, we investigated the effects of chronic subcutaneous (sc) administration of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ) on arterial pressure, autonomic modulation of arterial pressure, hypothalamic expression of AT1 receptors and neuroinflammatory markers and fluid balance in 2-kidney, 1clip (2K1C) renovascular hypertensive rats.

Materials And Methods: Male Holtzman rats with a clip occluding partially the left renal artery and chronic sc injections of ATZ were used.

The carotid body: A novel key player in neuroimmune interactions.

The idea that the nervous system communicates with the immune system to regulate physiological and pathological processes is not new. However, there is still much to learn about how these interactions occur under different conditions. The carotid body (CB) is a sensory organ located in the neck, classically known as the primary sensor of the oxygen (O) levels in the organism of mammals.

The carotid body detects circulating tumor necrosis factor-alpha to activate a sympathetic anti-inflammatory reflex.

Recent evidence has suggested that the carotid bodies might act as immunological sensors, detecting pro-inflammatory mediators and signalling to the central nervous system, which, in turn, orchestrates autonomic responses. Here, we confirmed that the TNF-α receptor type I is expressed in the carotid bodies of rats. The systemic administration of TNF-α increased carotid body afferent discharge and activated glutamatergic neurons in the nucleus tractus solitarius (NTS) that project to the rostral ventrolateral medulla (RVLM), where many pre-sympathetic neurons reside.

ANG II and Aldosterone Acting Centrally Participate in the Enhanced Sodium Intake in Water-Deprived Renovascular Hypertensive Rats.

Renovascular hypertension is a type of secondary hypertension caused by renal artery stenosis, leading to an increase in the renin-angiotensin-aldosterone system (RAAS). Two-kidney, 1-clip (2K1C) is a model of renovascular hypertension in which rats have an increased sodium intake induced by water deprivation (WD), a common situation found in the nature. In addition, a high-sodium diet in 2K1C rats induces glomerular lesion.

Intracranial Pressure During the Development of Renovascular Hypertension.

[Figure: see text].

Lesion of Serotonergic Afferents to the Retrotrapezoid Nucleus Impairs the Tachypneic Response to Hypercapnia in Unanesthetized Animals.

Hypercapnia promotes an increase in pulmonary ventilation due to the stimulation of brainstem chemosensory cells that are connected to the respiratory network. Among these cells are the raphe serotonergic neurons which widely send projections to distinct central respiratory compartments. Nevertheless, the physiological role of specific raphe serotonergic projections to other chemosensitive sites on the emergence of hypercapnia ventilatory response in vivo still remains to be elucidated.

Anti-hypertensive effect of hydrogen peroxide acting centrally.

Intracerebroventricular (icv) injection of hydrogen peroxide (HO) or the increase of endogenous HO centrally produced by catalase inhibition with 3-amino-1,2,4-triazole (ATZ) injected icv reduces the pressor responses to central angiotensin II (ANG II) in normotensive rats. In the present study, we investigated the changes in the arterial pressure and in the pressor responses to ANG II icv in spontaneously hypertensive rats (SHRs) and 2-kidney, 1-clip (2K1C) hypertensive rats treated with HO injected icv or ATZ injected icv or intravenously (iv). Adult male SHRs or Holtzman rats (n = 5-10/group) with stainless steel cannulas implanted in the lateral ventricle were used.

Renovascular hypertension elevates pulmonary ventilation in rats by carotid body-dependent mechanisms.

The two kidney-one clip (2K1C) renovascular hypertension depends on the renin-angiotensin system and sympathetic overactivity. The maintenance of 2K1C hypertension also depends on inputs from the carotid bodies (CB), which when activated stimulate the respiratory activity. In the present study, we investigated the importance of CB afferent activity for the ventilatory responses in 2K1C hypertensive rats and for phrenic and hypoglossal activities in in situ preparations of normotensive rats treated with angiotensin II.

Physiological and Transcriptomic Changes in the Hypothalamic-Neurohypophysial System after 24 h of Furosemide-Induced Sodium Depletion.

Background/aims: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion.

Methods: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h.

Modulation of hypercapnic respiratory response by cholinergic transmission in the commissural nucleus of the solitary tract.

The nucleus of the solitary tract (NTS) is an important area of the brainstem that receives and integrates afferent cardiorespiratory sensorial information, including those from arterial chemoreceptors and baroreceptors. It was described that acetylcholine (ACh) in the commissural subnucleus of the NTS (cNTS) promotes an increase in the phrenic nerve activity (PNA) and antagonism of nicotinic receptors in the same region reduces the magnitude of tachypneic response to peripheral chemoreceptor stimulation, suggesting a functional role of cholinergic transmission within the cNTS in the chemosensory control of respiratory activity. In the present study, we investigated whether cholinergic receptor antagonism in the cNTS modifies the sympathetic and respiratory reflex responses to hypercapnia.

Catalase blockade reduces the pressor response to central cholinergic activation.

Intracerebroventricular (icv) injection of hydrogen peroxide (HO), a reactive oxygen species, or the blockade of catalase (enzyme that degrades HO into HO and O) with icv injection of 3-amino-1,2,4-triazole (ATZ) reduces the pressor effects of angiotensin II also injected icv. In the present study, we investigated the effects of ATZ injected icv or intravenously (iv) on the pressor responses induced by icv injections of the cholinergic agonist carbachol, which similar to angiotensin II induces pressor responses that depend on sympathoexcitation and vasopressin release. In addition, the effects of HO icv on the pressor responses to icv carbachol were also tested to compare with the effects of ATZ.

Centrally acting adrenomedullin in the long-term potentiation of sympathetic vasoconstrictor activity induced by intermittent hypoxia in rats.

New Findings: What is the central question of this study? Adrenomedullin in the rostral ventrolateral medulla (RVLM) increases sympathetic activity; given that adrenomedullin is released during hypoxia, what are the effects of its agonism and antagonism in the RVLM after chronic intermitent hypoxia (CIH) exposure? What is the main finding and its importance? CIH exposure sensitizes adrenomedullin-dependent mechanisms in the RVLM, supporting its role as a sympathoexcitatory neuromodulator. A novel mechanism was identified for the generation of sympathetic overdrive and hypertension associated with hypoxia, providing potential guidance on new therapeutic approaches for controlling sympathetic hyperactivity in diseases such as sleep apnoea and neurogenic hypertension.

Abstract: Adrenomedullin in the rostral ventrolateral medulla (RVLM) has been shown to increase sympathetic activity whereas the antagonism of its receptors inhibited this autonomic activity lowering blood pressure in conditions of hypertension.

Importance of AT1 and AT2 receptors in the nucleus of the solitary tract in cardiovascular responses induced by a high-fat diet.

A high-fat diet (HFD) induces an increase in arterial pressure and a decrease in baroreflex function, which may be associated with increased expression of angiotensin type 1 receptor (AT1R) and pro-inflammatory cytokine genes and reduced expression of the angiotensin type 2 receptor (AT2R) gene within the nucleus of the solitary tract (NTS), a key area of the brainstem involved in cardiovascular control. Thus, in the present study, we evaluated the changes in arterial pressure and gene expression of components of the renin-angiotensin system (RAS) and neuroinflammatory markers in the NTS of rats fed a HFD and treated with either an AT1R blocker or with virus-mediated AT2R overexpression in the NTS. Male Holtzman rats (300-320 g) were fed either a standard rat chow diet (SD) or HFD for 6 weeks before commencing the tests.

Importance of the commissural nucleus of the solitary tract in renovascular hypertension.

The rodent renovascular hypertension model has been used to investigate the mechanisms promoting hypertension. The importance of the carotid body for renovascular hypertension has been demonstrated. As the commissural NTS (cNTS) is the first synaptic site in the central nervous system that receives information from carotid body chemoreceptors, we evaluated the contribution of cNTS to renovascular hypertension in the present study.

Endogenous hydrogen peroxide affects antidiuresis to cholinergic activation in the medial septal area.

Cholinergic activation of the medial septal area (MSA) with carbachol produces thirst, natriuresis and antidiuresis. Hydrogen peroxide (HO) injected into the medial septal area (MSA) impairs behavioral and renal responses induced by carbachol at the same site, suggesting the exogenous HO may modulate the responses to cholinergic activation in the MSA. In the present study, we investigated if the accumulation of endogenous HO in the MSA after the injection of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ) also affects cholinergic responses.

Central muscarinic and LPBN mechanisms on sodium intake.

Central cholinergic activation stimulates water intake, but also NaCl intake when the inhibitory mechanisms are blocked with injections of moxonidine (α adrenergic/imidazoline agonist) into the lateral parabrachial nucleus (LPBN). In the present study, we investigated the involvement of central M and M muscarinic receptors on NaCl intake induced by pilocarpine (non-selective muscarinic agonist) intraperitoneally combined with moxonidine into the LPBN or by muscimol (GABA agonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN and in the lateral ventricle were used.

High-fat diet increases respiratory frequency and abdominal expiratory motor activity during hypercapnia.

Breathing disorders are commonly observed in association with obesity. Here we tested whether high-fat diet (HFD) impairs the chemoreflex ventilatory response. Male Holtzman rats (300-320 g) were fed with standard chow diet (SD) or HFD for 12 weeks.

Opioid and α adrenergic mechanisms are activated by GABA agonists in the lateral parabrachial nucleus to induce sodium intake.

The activation of GABA, opioid or α adrenergic mechanisms in the lateral parabrachial nucleus (LPBN) facilitates hypertonic NaCl intake in rats. In the present study, we combined opioid or α adrenergic antagonists with GABA agonists into the LPBN in order to investigate if NaCl intake caused by GABAergic activation in normohydrated rats depends on opioid or α-adrenergic mechanisms in this area. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used.

Enhanced angiotensin II induced sodium appetite in renovascular hypertensive rats.

Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin-angiotensin system and an initial transitory increase in daily water and NaCl intake. However, the dipsogenic and natriorexigenic responses to angiotensin II (ANG II) have not been tested yet in 2K1C rats. Therefore, in the present study, we evaluated water and 0.