Intermittent hypoxia changes the interaction of the kinin-VEGF system and impairs myocardial angiogenesis in the hypertrophic heart.

Intermittent hypoxia (IH) is a feature of obstructive sleep apnea (OSA), a condition highly associated with hypertension-related cardiovascular diseases. Repeated episodes of IH contribute to imbalance of angiogenic growth factors in the hypertrophic heart, which is key in the progression of cardiovascular complications. In particular, the interaction between vascular endothelial growth factor (VEGF) and the kallikrein-kinin system (KKS) is essential for promoting angiogenesis.

Pattern of sympathetic vasomotor activity induced by GABAergic inhibition in the brain and spinal cord.

Background: Knowledge of the central areas involved in the control of sympathetic vasomotor activity has advanced in the last few decades. γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammal nervous system, and a microinjection of bicuculline, an antagonist of GABA type A (GABA-A) receptors, into the paraventricular nucleus of the hypothalamus (PVN) alters the pattern of sympathetic activity to the renal, splanchnic and lumbar territories. However, studies are needed to clarify the role of GABAergic inputs in other central areas involved in the sympathetic vasomotor activity.

Renal denervation reduces sympathetic overactivation, brain oxidative stress, and renal injury in rats with renovascular hypertension independent of its effects on reducing blood pressure.

The underlying mechanisms by which renal denervation (RD) decreases blood pressure (BP) remain incompletely understood. In this study, we investigated the effects of ischemic kidney denervation on different sympathetic outflows, brain and renal expression of angiotensin-II receptors, oxidative stress and renal function markers in the 2-kidney, 1-clip (2K-1C) rat model. Surgical RD was performed in Wistar male rats 4-5 weeks after clip implantation.

Chronic intermittent hypoxia induces changes on the expression and activity of neprilysin (EC 3.4.24.11) in the brain of rats.

Obstructive sleep apnea (OSA) is a frequent sleeping breathing disorder associated with cognitive impairments. Neprilysin (NEP) is responsible for degrading several substrates related to cognition; however, the effect of chronic intermittent hypoxia (CIH) on NEP is still unknown. This study aimed to evaluate the expression and activity of NEP in cognitive-related brain structures of rats submitted to CIH.

Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor gene expression, although not that of the protein itself, in the temporal cortex of rats.

Objective: Obstructive sleep apnea syndrome is mainly characterized by intermittent hypoxia (IH) during sleep, being associated with several complications. Exposure to IH is the most widely used animal model of sleep apnea, short-term IH exposure resulting in cognitive and neuronal impairment. Pigment epithelium-derived factor (PEDF) is a hypoxia-sensitive factor acting as a neurotrophic, neuroprotective, and antiangiogenic agent.

Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension.

Background: Although angiotensin II (Ang II) is essential to the development of renovascular hypertension, aldosterone plays a role as well. Recent studies have demonstrated a cross-talk between Ang II type 1 and mineralocorticoid receptors in the brain and kidneys. However, the role of aldosterone in the autonomic and renal dysfunction of renovascular hypertension is not well understood.

Validation of housekeeping genes in the brains of rats submitted to chronic intermittent hypoxia, a sleep apnea model.

Obstructive sleep apnea (OSA) is a syndrome characterized by intermittent nocturnal hypoxia, sleep fragmentation, hypercapnia and respiratory effort, and it has been associated with several complications, such as diabetes, hypertension and obesity. Quantitative real-time PCR has been performed in previous OSA-related studies; however, these studies were not validated using proper reference genes. We have examined the effects of chronic intermittent hypoxia (CIH), which is an experimental model mainly of cardiovascular consequences of OSA, on reference genes, including beta-actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hypoxanthine guanine phosphoribosyl transferase and eukaryotic 18S rRNA, in different areas of the brain.

Interconnectivity of sympathetic and sleep networks is mediated through reduction of gamma aminobutyric acidergic inhibition in the paraventricular nucleus.

Chronic short sleep duration has been linked to sympathoexcitation and increased risk of cardiovascular disease. The central nervous system plays an important role in the regulation of sympathetic activity. Thus, the present study evaluates the pre-autonomic neurones in the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla after sleep restriction using various protein expression measurements and electrophysiological approaches.

Whole blood hypoxia-related gene expression reveals novel pathways to obstructive sleep apnea in humans.

In this study, our goal was to identify the key genes that are associated with obstructive sleep apnea (OSA). Thirty-five volunteers underwent full in-lab polysomnography and, according to the sleep apnea hypopnea index (AHI), were classified into control, mild-to-moderate OSA and severe OSA groups. Severe OSA patients were assigned to participate in a continuous positive airway pressure (CPAP) protocol for 6 months.

Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain.

Many studies indicate that thimet oligopeptidase (EC3.4.24.

Cocaine administration increases angiotensin I-converting enzyme (ACE) expression and activity in the rat striatum and frontal cortex.

Some central effects of cocaine administration seem to be related to angiotensin II (Ang II) or its metabolites. Nonetheless, it is still an open question whether or not the levels of angiotensin I-converting enzyme (ACE), the main Ang II generating enzyme, are modified by cocaine administration. To evaluate the effect of acute and subchronic cocaine administration on ACE activity and mRNA expression, male rats were randomly assigned to saline or cocaine group.

Sympathetic and angiotensinergic responses mediated by paradoxical sleep loss in rats.

Introduction: Recent investigations over the past decade have linked the development of hypertension to sleep loss, although the mechanisms underlying this association are still under scrutiny. To determine the relationship between sleep deprivation and cardiovascular dysfunction, we examined the effects of paradoxical sleep deprivation on heart rate, blood pressure, sympathetic nerve activity (SNA) and their consequences in the blood renin-angiotensin system.

Materials And Methods: Wistar-Hannover male rats were randomly assigned to three experimental groups: 1) control, 2) paradoxical sleep deprivation for 24 h and 3) paradoxical sleep deprivation for 96 h.

Differential sympathetic activation induced by intermittent hypoxia and sleep loss in rats: Action of angiotensin (1-7).

The present study attempted to evaluate the effects of chronic intermittent hypoxia (CIH) associated with sleep restriction in hemodynamic parameters and the plasma renin-angiotensin system. Wistar-Hannover rats were submitted to isolated CIH exposure (1000-1600 h), sleep restriction (1600-1000 h), defined as 18-h paradoxical sleep deprivation followed by 6-h sleep permission period and CIH associated to sleep restriction for 21 days. The CIH and sleep restriction group showed a preferential increase in renal sympathetic nervous system (rSNA) associated with a reduction in plasma angiotensin (1-7) concentrations.

Paradoxical sleep deprivation influences sexual behavior in female rats.

Introduction: Sleep disturbances are a frequent complaint in women and are often attributed to hormonal fluctuations during the menstrual cycle. Rodents have been used as models to examine the effects of sleep deprivation on hormonal and behavioral changes. Among the many comorbidities common to sleep disorders, sexual behavior remains the least well studied.

Intermittent hypoxia and sleep restriction: motor, cognitive and neurochemical alterations in rats.

The present study evaluated the effects of intermittent hypoxia (IH) and sleep restriction (SR) upon motor and cognitive function in rats. Also evaluated were catecholamine concentrations and tyrosine hydroxylase (TH) protein expression in different regions of the forebrain. Wistar Hannover rats were submitted to IH for 4 days or 21 days (2 min room air to 2 min 10% O(2) for 10:00-16:00 h), followed by SR for 18 h (16:00-10:00 h).

Possible participation of D3 and D4 dopaminergic receptors on genital reflexes induced by cocaine in paradoxical sleep deprived male rats.

Previous studies have demonstrated that paradoxical sleep deprivation (PSD) potentiates cocaine-induced genital reflexes in male rats and both D1 and D2 receptors may play a role in those effects, and to examine the possibility that such might involve other dopaminergic receptors, we investigated the effects of D3 and D4 receptor subtype antagonists on cocaine-induced reflexes in sleep-deprived rats. Separate groups of PSD rats received saline, D3 (U9919A; 0.75, 1.

Distinct behavioral and neurochemical alterations induced by intermittent hypoxia or paradoxical sleep deprivation in rats.

The current study investigated the effects of paradoxical sleep deprivation and intermittent hypoxia by examining whether a combination of the two would induce anxiety-like alterations in behavior. The neurochemical effects of these manipulations were investigated by measuring cortical, striatal and hippocampal monoamine concentrations. Wistar Hannover rats were submitted to subchronic (3 days) intermittent hypoxia exposure (alternating cycles of 2 min room air-2 min 10% O2 from 0700-1900 h) and paradoxical sleep deprivation using the single platform method.

Influence of chronic cocaine treatment and sleep deprivation on sexual behavior and neurogenesis of the male rat.

The present study investigated the influence of chronic cocaine treatment on genital reflexes associated with paradoxical sleep deprivation (PSD), and possible alterations in hippocampus neurogenesis of the male rat. At 21 days of age, the rats were distributed into two groups and injected with saline or cocaine (7 mg/kg, three times a week for 12 weeks). At age 90 days, they were submitted to a four-day period of PSD (PSD groups) or maintained in home-cages (control groups), challenged with saline or cocaine administration, and placed in observation cages to assess genital reflexes.

Effects of different substance misuse in genital reflexes of paradoxical sleep deprived male rats.

As psychostimulants are widely abused, their neurochemical and behavioral effects have been extensively studied for many years. Our previous data demonstrate that paradoxical sleep deprivation (PSD) enhances drug-induced penile erection and ejaculation. PSD in association to drugs of abuse like cocaine potentiated genital reflexes in male rats.

Involvement of nitric oxide in cocaine-induced erections and ejaculations after paradoxical sleep deprivation.

Objectives: As nitric oxide (NO) is involved in penile erectile (PE) function and also influences the sleep-wake cycle, we speculated that NO could play a role in PE and ejaculation of paradonical sleep deprivation (PSD) rats.

Methods: Animals were pretreated with N(G)-nitro-L-arginine methyl ester (L-NAME, ip) and L-arginine (ip and icv) prior to saline or cocaine injection.

Results: Cocaine-induced PE in 90% of PSD rats, 60% of which ejaculated.

Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats.

Since studies suggest that both hypoxia and sleep fragmentation are related to cardiovascular alterations induced by obstructive sleep apnea, the present study was designed to evaluate the effects of hypoxia, sleep deprivation, and their combination on biochemical blood parameters in rats. In subchronic experiments (4 days), rats were exposed to intermittent hypoxia (IH) during the light period (2min room air-2min 10% O(2) for 12h/day) and/or paradoxical sleep deprivation (PSD, 24h/day). Consequences of chronic intermittent hypoxia (CIH) exposure were examined after 21 consecutive days of hypoxia protocol from 10:00 to 16:00 followed by a sleep restriction (SR) period of 18h (16:00-10:00).

Intra-nigral MPTP lesion in rats: behavioral and autoradiography studies.

The present study investigated the motor response and possible changes in binding to D1 and D2 receptors after intra-nigral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion on rats. The results indicated that MPTP-lesioned rats exhibited a significant reduction in locomotion and rearing frequencies observed in an open field 24 h after surgery. However, at 7 and 14 days after surgery the MPTP-lesioned rats showed a significant increase in locomotion in comparison to the control groups, as well as a decrease in immobility time.

Acute cocaine effects in paradoxical sleep deprived male rats.

Cocaine is a psychomotor drug known to cause behavioural alterations. This study was conducted to characterize behavioural response to acute cocaine injection (7 mg/kg, ip) in paradoxical sleep deprived (PSD) male rats since sleep deprivation is also associated with several behavioural alterations. Cocaine or vehicle was administered to rats at the end of a 4-day period of sleep deprivation, and in home-cage control animals.

Phosphatidylserine: an antidepressive or a cognitive enhancer?

The aim of the present study was to evaluate the putative antidepressive and cognitive enhancer effects of phosphatidylserine (BC-PS). The antidepressive effect of BC-PS (50, 100 or 200 mg/kg), compared to saline or imipramine (IMI; 25 mg/kg), was studied in the forced swimming test in rats. These drugs were administered 1 and 8 h after training and 1 h before the test.

Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats.

The present study investigated the effects of intranigral MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) infusion on rats treated with phosphatidylserine and evaluated in two memory tasks and on striatal dopamine levels. The results indicated that MPTP produced a significant decrease in the avoidance number in comparison to sham-operated and non-operated rats submitted to a two-way avoidance task. MPTP-lesioned rats exhibited an increase in the latencies to find the platform in cued version of the water maze in comparison to sham-operated and non-operated animals.