Chronic intermittent hypoxia-induced hypertension: the impact of sex hormones.

Obstructive sleep apnea, a common form of sleep-disordered breathing, is characterized by intermittent cessations of breathing that reduce blood oxygen levels and contribute to the development of hypertension. Hypertension is a major complication of obstructive sleep apnea that elevates the risk of end-organ damage. Premenopausal women have a lower prevalence of obstructive sleep apnea and cardiovascular disease than men and postmenopausal women, suggesting that sex hormones play a role in the pathophysiology of sleep apnea-related hypertension. The lack of protection in men and postmenopausal women implicates estrogen and progesterone as protective agents but testosterone as a permissive agent in sleep apnea-induced hypertension. A better understanding of how sex hormones contribute to the pathophysiology of sleep apnea-induced hypertension is important for future research and possible hormone-based interventions. The effect of sex on the pathophysiology of sleep apnea and associated intermittent hypoxia-induced hypertension is of important consideration in the screening, diagnosis, and treatment of the disease and its cardiovascular complications. This review summarizes our current understanding of the impact of sex hormones on blood pressure regulation in sleep apnea with a focus on sex differences.

Correction of the pelvic incidence using a bilateral extending pelvic osteotomy: a proof of concept study.

INTRODUCTION: The aim of this proof of concept human cadaver study was to quantify the effect of a bilateral extending pelvic osteotomy (BEPO) on pelvic incidence (PI) as a potential alternative for a pedicle subtraction osteotomy (PSO) in patients with severe spinal sagittal malalignment. MATERIALS AND METHODS: 10 fresh frozen human cadavers were treated with the BEPO technique. CT images were made before and after the osteotomy and pure sagittal images were created on which PI was measured. RESULTS: The mean pre-osteotomy PI was 47.9° (range 36.4-63.9) and the mean post-osteotomy PI was 36.5° (range 22.1-54.4). The mean correction was - 10.4° with a range of - 8.4° to - 17.3° (p = 0.03), which resulted in a mean decrease of 23% in the PI (range 16-42). CONCLUSIONS: There was a feasible and effective correction of PI using the BEPO technique on the os ilium. This was a preliminary cadaveric study. No conclusions could be made on global sagittal alignment. We postulate that an extending osteotomy of the ilium could be a potential alternative for a PSO reducing the complexity of spine surgery in patients with severe spinal sagittal malalignment.

Chronic intermittent hypoxia enhances glycinergic inhibition in nucleus tractus solitarius.

Chronic intermittent hypoxia (CIH), an animal model of sleep apnea, has been shown to alter the activity of second-order chemoreceptor neurons in the caudal nucleus of the solitary tract (cNTS). Although numerous studies have focused on excitatory plasticity, few studies have explored CIH-induced plasticity impacting inhibitory inputs to NTS neurons, and the roles of GABAergic and glycinergic inputs on heightened cNTS excitability following CIH are unknown. In addition, changes in astrocyte function may play a role in cNTS plasticity responses to CIH. This study tested the effects of a 7-day CIH protocol on miniature inhibitory postsynaptic currents (mIPSCs) in cNTS neurons receiving chemoreceptor afferents. Normoxia-treated rats primarily displayed GABA mIPSCs, whereas CIH-treated rats exhibited a shift toward combined GABA/glycine-mediated mIPSCs. CIH increased glycinergic mIPSC amplitude and area. This shift was not observed in dorsal motor nucleus of the vagus neurons or cNTS cells from females. Immunohistochemistry showed that strengthened glycinergic mIPSCs were associated with increased glycine receptor protein and were dependent on receptor trafficking in CIH-treated rats. In addition, CIH altered astrocyte morphology in the cNTS, and inactivation of astrocytes following CIH reduced glycine receptor-mediated mIPSC frequency and overall mIPSC amplitude. In cNTS, CIH produced changes in glycine signaling that appear to reflect increased trafficking of glycine receptors to the cell membrane. Increased glycine signaling in cNTS associated with CIH also appears to be dependent on astrocytes. Additional studies will be needed to determine how CIH influences glycine receptor expression and astrocyte function in cNTS.NEW & NOTEWORTHY Chronic intermittent hypoxia (CIH) has been used to mimic the hypoxemia associated with sleep apnea and determine how these hypoxemias influence neural function. The nucleus of the solitary tract is the main site for chemoreceptor input to the CNS, but how CIH influences NTS inhibition has not been determined. These studies show that CIH increases glycine-mediated miniature IPSCs through mechanisms that depend on protein trafficking and astrocyte activation.

Remote ischaemic conditioning: defining critical criteria for success-report from the 11th Hatter Cardiovascular Workshop.

The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2-ERIC-PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.

Norepinephrine innervation of the supraoptic nucleus contributes to increased copeptin and dilutional hyponatremia in male rats.

Dilutional hyponatremia associated with liver cirrhosis is due to inappropriate release of arginine vasopressin (AVP). Elevated plasma AVP causes water retention resulting in a decrease in plasma osmolality. Cirrhosis, in this study caused by ligation of the common bile duct (BDL), leads to a decrease in central vascular blood volume and hypotension, stimuli for nonosmotic AVP release. The A1/A2 neurons stimulate the release of AVP from the supraoptic nucleus (SON) in response to nonosmotic stimuli. We hypothesize that the A1/A2 noradrenergic neurons support chronic release of AVP in cirrhosis leading to dilutional hyponatremia. Adult, male rats were anesthetized with 2-3% isoflurane (mixed with 95% O2/5% CO2) and injected in the SON with anti-dopamine ß-hydroxylase (DBH) saporin (DSAP) or vehicle followed by either BDL or sham surgery. Plasma copeptin, osmolality, and hematocrit were measured. Brains were processed for ΔFosB, dopamine ß-hydroxylase (DBH), and AVP immunohistochemistry. DSAP injection: 1) significantly reduced the number of DBH immunoreactive A1/A2 neurons (A1, P < 0.0001; A2, P = 0.0014), 2) significantly reduced the number of A1/A2 neurons immunoreactive to both DBH and ΔFosB positive neurons (A1, P = 0.0015; A2, P < 0.0001), 3) reduced the number of SON neurons immunoreactive to both AVP and ΔFosB (P < 0.0001), 4) prevented the increase in plasma copeptin observed in vehicle-injected BDL rats (P = 0.0011), and 5) normalized plasma osmolality and hematocrit (plasma osmolality, P = 0.0475; hematocrit, P = 0.0051) as compared with vehicle injection. Our data suggest that A1/A2 neurons contribute to increased plasma copeptin and hypoosmolality in male BDL rats.

AT1a-dependent GABAA inhibition in the MnPO following chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) is associated with diurnal hypertension, increased sympathetic nerve activity (SNA), and increases in circulating angiotensin II (ANG II). In rats, CIH increases angiotensin type 1 (AT1a) receptor expression in the median preoptic nucleus (MnPO), and pharmacological blockade or viral knockdown of this receptor prevents CIH-dependent increases in diurnal blood pressure. The current study investigates the role of AT1a receptor in modulating the activity of MnPO neurons following 7 days of CIH. Male Sprague-Dawley rats received MnPO injections of an adeno-associated virus with an shRNA against the AT1a receptor or a scrambled control. Rats were then exposed to CIH for 8 h a day for 7 days. In vitro, loose patch recordings of spontaneous action potential activity were made from labeled MnPO neurons in response to brief focal application of ANG II or the GABAA receptor agonist muscimol. In addition, MnPO K-Cl cotransporter isoform 2 (KCC2) protein expression was assessed using Western blot. CIH impaired the duration but not the magnitude of ANG II-mediated excitation in the MnPO. Both CIH and AT1a knockdown also impaired GABAA-mediated inhibition, and CIH with AT1a knockdown produced GABAA-mediated excitation. Recordings using the ratiometric Cl- indicator ClopHensorN showed CIH was associated with Cl- efflux in MnPO neurons that was associated with decreased KCC2 phosphorylation. The combination of CIH and AT1a knockdown attenuated reduced KCC2 phosphorylation seen with CIH alone. The current study shows that CIH, through the activity of AT1a receptors, can impair GABAA-mediated inhibition in the MnPO and contribute to sustained hypertension.

Role of angiotensin II in chronic intermittent hypoxia-induced hypertension and cognitive decline.

Sleep apnea is characterized by momentary interruptions in normal respiration and leads to periods of decreased oxygen, or intermittent hypoxia. Chronic intermittent hypoxia is a model of the hypoxemia associated with sleep apnea and results in a sustained hypertension that is maintained during normoxia. Adaptations of the carotid body and activation of the renin-angiotensin system may contribute to the development of hypertension associated with chronic intermittent hypoxia. The subsequent activation of the brain renin-angiotensin system may produce changes in sympathetic regulatory neural networks that support the maintenance of the hypertension associated with intermittent hypoxia. Hypertension and sleep apnea not only increase risk for cardiovascular disease but are also risk factors for cognitive decline and Alzheimer's disease. Activation of the angiotensin system could be a common mechanism that links these disorders.

Terahertz magnetoplasmon resonances in coupled cavities formed in a gated two-dimensional electron gas.

We report on both experiments and theory of low-terahertz frequency range (up to 400 GHz) magnetoplasmons in a gated two-dimensional electron gas at low (<4K) temperatures. The evolution of magnetoplasmon resonances was observed as a function of magnetic field at frequencies up to ∼400 GHz. Full-wave 3D simulations of the system predicted the spatial distribution of plasmon modes in the 2D channel, along with their frequency response, allowing us to distinguish those resonances caused by bulk and edge magnetoplasmons in the experiments. Our methodology is anticipated to be applicable to the low temperature (<4K) on-chip terahertz measurements of a wide range of other low-dimensional mesoscopic systems.

Diagnosis and management of osteoporosis in chronic kidney disease stages 4 to 5D: a call for a shift from nihilism to pragmatism.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) CKD-MBD working group, in collaboration with the Committee of Scientific Advisors of the International Osteoporosis Foundation, published a position paper for the diagnosis and management of osteoporosis in patients with CKD stages 4-5D (eGFR < 30 ml/min 1.73 m2). The present article reports and summarizes the main recommendations included in this 2021 document. The following areas are reviewed: diagnosis of osteoporosis; risk factors for fragility fractures; fracture risk assessment; intervention thresholds for pharmacological intervention; general and pharmacological management of osteoporosis; monitoring of treatment, and systems of care, all in patients with CKD stages 4-5D. Guidance is provided for clinicians caring for CKD stages 4-5D patients with osteoporosis, allowing for a pragmatic individualized diagnostic and therapeutic approach as an alternative to current variations in care and treatment nihilism.

Sex Differences in the Regulation of Vasopressin and Oxytocin Secretion in Bile Duct-Ligated Rats.

INTRODUCTION: Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. No previous studies have addressed sex differences in hyponatremia in liver failure animal models. OBJECTIVE: This study addressed this gap in our understanding of the potential sex differences in hyponatremia associated with increased AVP secretion. METHODS: This study tested the role of sex in the development of hyponatremia using adult male, female, and ovariectomized (OVX) female bile duct-ligated (BDL) rats. RESULTS: All BDL rats had significantly increased liver to body weight ratios compared to sham controls. Male BDL rats had hyponatremia with significant increases in plasma copeptin and FosB expression in supraoptic AVP neurons compared to male shams (all p < 0.05; 5-7). Female BDL rats did not become hyponatremic or demonstrate increased supraoptic AVP neuron activation and copeptin secretion compared to female shams. Plasma oxytocin was significantly higher in female BDL rats compared to female sham (p < 0.05; 6-10). This increase was not observed in male BDL rats. Ovariectomy significantly decreased plasma estradiol in sham rats compared to intact female sham (p < 0.05; 6-10). However, circulating estradiol was significantly elevated in OVX BDL rats compared to the OVX and female shams (p < 0.05; 6-10). Adrenal estradiol, testosterone, and dehydroepiandrosterone (DHEA) were measured to identify a possible source of circulating estradiol in OVX BDL rats. The OVX BDL rats had significantly increased adrenal estradiol along with significantly decreased adrenal testosterone and DHEA compared to OVX shams (all p < 0.05; 6-7). Plasma osmolality, hematocrit, copeptin, and AVP neuron activation were not significantly different between OVX BDL and OVX shams. Plasma oxytocin was significantly higher in OVX BDL rats compared to OVX sham. CONCLUSIONS: Our results show that unlike male BDL rats, female and OVX BDL rats did not develop hyponatremia, supraoptic AVP neuron activation, or increased copeptin secretion compared to female shams. Adrenal estradiol might have compensated for the lack of ovarian estrogens in OVX BDL rats.

Tolerance of three fungal species to lithium and cobalt: Implications for bioleaching of spent rechargeable Li-ion batteries.

AIMS: This paper aims to quantify the growth and organic acid production of Aspergillus niger, Penicillium chrysogenum and Penicillium simplicissimum when these fungi are exposed to varying levels of lithium (Li) and cobalt (Co). The study also tests whether pre-exposing the fungi to these metals enables the fungi to develop tolerance to Li or Co. METHODS AND RESULTS: When cultures of A. niger, P. chrysogenum or P. simplicissimum were exposed to 250 mg l-1 of Li or Co, biomass production and excretion of organic acids were significantly inhibited after 5 days of growth compared to cultures grown in the absence of these metals. Pre-exposing cultures of A. niger to 250 mg l-1 of Li or Co for 20 days significantly increased biomass production when the fungus was subsequently sub-cultured into 250 or 500 mg l-1 of Li or Co. However, pre-exposure of P. chrysogenum or P. simplicissimum to 250 mg l-1 of Li or Co for 20 days did not increase biomass production. CONCLUSIONS: Aspergillus niger, but not the Penicillium species, developed tolerance to Li and to Co during the 20-day pre-exposure period. Therefore, processes that utilize fungal bioleaching with A. niger to mobilize and recover valuable metals such as Li or Co should consider a pre-exposure step for fungi to improve their tolerance to metal toxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: Fungi may have the ability to extract valuable metals such as Li and Co from spent rechargeable batteries. However, the toxicity of the extracted metals can inhibit fungal growth and organic acid production. Pre-exposure to metals may alleviate toxicity for some fungal species. This knowledge can be used to improve the design of bioleaching protocols, increasing the potential for fungal bioleaching to become an economical and environmentally friendly method of recovering Li and Co from spent batteries.

Current and future best practice in imaging, staging, and response assessment for Non-Hodgkin's lymphomas: the Specialist Integrated Haematological Malignancy Imaging Reporting (SIHMIR) paradigm shift.

Non-Hodgkin's lymphoma (NHL) encompasses over 40 different haematological malignancies, including low and high-grade neoplasms, such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) respectively. A key clinical issue in the context of NHL is delayed and inaccurate diagnosis, which contributes adversely to patient morbidity and mortality. This article will address relevant imaging aspects, with particular reference to advancements in NHL imaging, including computed tomography (CT), integrated positron-emission tomography (PET)-CT, and magnetic resonance imaging (MRI). We provide multiparametric (anato-functional) imaging display items, including histological correlation. We will also introduce our original concept of "Specialist Integrated Haematological Malignancy Imaging Reporting" (SIHMIR), a paradigm shift in lymphoma radiology.

Gq DREADD activation of CaMKIIa MnPO neurons stimulates nitric oxide activity.

Designer receptors exclusively activated by designer drugs (DREADDs) modify cellular activity following administration of the exogenous ligand clozapine-N-oxide (CNO). However, some reports indicate CNO may have off-target effects. The current studies investigate the use of Gq DREADDs in CaMKIIa-expressing neurons in the median preoptic nucleus (MnPO). Male Sprague-Dawley rats (250 g) anesthetized with isoflurane were stereotaxically microinjected in the MnPO with the Gq DREADD (AAV5-CaMKIIa-HM3D-mCherry) or control virus (AAV5-CaMKIIa-mCherry). Following a 2-wk recovery, rats were used for either immunohistochemical Fos analysis or in vitro patch-clamp electrophysiology. In Gq DREADD-injected rats, CNO induced significant increases in Fos staining in the MnPO and in regions that receive direct or indirect projections from the MnPO. In electrophysiological studies, CNO depolarized and augmented firing frequency in both Gq DREADD-positive neurons (Gq DREADD) as well as unlabeled MnPO neurons in slices from Gq DREADD-injected rats (Gq DREADDx). Gq DREADDx neurons also displayed increases in spontaneous postsynaptic current (sPSC) frequency in response to CNO. Additionally, CaMKIIa-positive MnPO neurons, which also express nitric oxide synthase (NOS), were treated with Nω-nitro-l-arginine (l-NNA; competitive inhibitor of NOS) and hemoglobin (NO scavenger) to assess the role of NO in Gq DREADDx neuron recruitment. Both l-NNA and hemoglobin blocked CNO-induced effects in Gq DREADDx neurons without affecting Gq DREADD neurons. These findings indicate that Gq DREADD-mediated activation of CaMKIIa/NOS expressing neurons in the MnPO can influence the activity of neighboring neurons. Future studies utilizing the use of Gq DREADDs will need to consider the potential recruitment of additional cell populations.NEW & NOTEWORTHY Rats were injected in the median preoptic nucleus (MnPO) with either an adeno-associated virus (AAV) and excitatory (Gq) designer receptor exclusively activated by designer drugs (DREADD) construct or a control AAV. In the Gq DREADD-injected rats only, clozapine-N-oxide (CNO) increased Fos staining in the MnPO and its targets and increased neuron action potential frequency. In electrophysiology experiments with slices with DREADD cells, unlabeled cells were activated and this was likely due to nitric oxide release by the DREADD cells.

Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats.

Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250-300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension.NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.

Brain-Derived Neurotrophic Factor and Supraoptic Vasopressin Neurons in Hyponatremia.

Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. The mechanisms causing dysregulation of AVP secretion are unknown. Our hypothesis is that inappropriate AVP release associated with liver failure is due to increased brain-derived neurotrophic factor (BDNF) in the supraoptic nucleus (SON). BDNF diminishes GABAA inhibition in SON AVP neurons by increasing intracellular chloride through tyrosine receptor kinase B (TrkB) activation and downregulation of K+/Cl- cotransporter 2 (KCC2). This loss of inhibition could increase AVP secretion. This hypothesis was tested using shRNA against BDNF (shBDNF) in the SON in bile duct ligated (BDL) male rats. All BDL rats had significantly increased liver weight (p < 0.05; 6-9) compared to shams. BDL rats with control -shRNA injections (BDL scrambled [SCR]) developed hyponatremia with increased plasma AVP and copeptin (CPP; all p < 0.05; 6-9) compared to sham groups. This is the first study to show that phosphorylation of TrkB is significantly increased along with significant decrease in phosphorylation of KCC2 in BDL SCR rats compared to the sham rats (p < 0.05;6-8). Knockdown of BDNF in the SON of BDL rats (BDL shBDNF) significantly increased plasma osmolality and hematocrit compared to BDL SCR rats (p < 0.05; 6-9). The BDL shBDNF rats had significant (p < 0.05; 6-9) decreases in plasma AVP and CPP concentration compared to BDL SCR rats. The BDNF knockdown also significantly blocked the increase in TrkB phosphorylation and decrease in KCC2 phosphorylation (p < 0.05; 6-8). The results indicate that BDNF produced in the SON contributes to increased AVP secretion and hyponatremia during liver failure.

Can Brief Email Guidance Enhance the Effects of an Internet Intervention for People with Problematic Alcohol Use? A Randomized Controlled Trial.

BACKGROUND: Some research suggests that internet interventions aimed at people with problematic alcohol use are more effective when provided with guidance from a therapist or coach. Purpose/Objectives: This trial intended to compare the effects of a previously evaluated internet intervention for people with problematic alcohol use when delivered with or without brief email guidance. Methods: Using online advertising, 238 participants, 18 years or older, were recruited and randomized to receive access to the Internet intervention Alcohol Help Center with or without brief email guidance from a health educator. The guidance consisted of at least four structured, slightly individualized emails delivered during the first two weeks after randomization. Participants were followed up at 3 and 6 months. Results: Number of log-ins did not differ significantly between groups throughout the follow-up period. The follow-up rate at 6 months was 47.0%. Generalized estimating equations run on the primary (standard drinks in preceding week/heavy drinking days in preceding week) and secondary outcome variables (AUDIT, AUDIT-C, quality of life) revealed no significant differences between the interventions on any of the outcomes. Conclusions/Importance: The study does not provide support for any added benefits of providing brief guidance via email in an internet intervention for problem drinkers.

Angiotensin type 1a receptors in the median preoptic nucleus support intermittent hypoxia-induced hypertension.

Chronic intermittent hypoxia (CIH) is a model of the hypoxemia from sleep apnea that causes a sustained increase in blood pressure. Inhibition of the central renin-angiotensin system or FosB in the median preoptic nucleus (MnPO) prevents the sustained hypertensive response to CIH. We tested the hypothesis that angiotensin type 1a (AT1a) receptors in the MnPO, which are upregulated by CIH, contribute to this hypertension. In preliminary experiments, retrograde tract tracing studies showed AT1a receptor expression in MnPO neurons projecting to the paraventricular nucleus. Adult male rats were exposed to 7 days of intermittent hypoxia (cycling between 21% and 10% O2 every 6 min, 8 h/day during light phase). Seven days of CIH was associated with a FosB-dependent increase in AT1a receptor mRNA without changes in the permeability of the blood-brain barrier in the MnPO. Separate groups of rats were injected in the MnPO with an adeno-associated virus containing short hairpin (sh)RNA against AT1a receptors to test their role in intermittent hypoxia hypertension. Injections of shRNA against AT1a in MnPO blocked the increase in mRNA associated with CIH, prevented the sustained component of the hypertension during normoxia, and reduced circulating advanced oxidation protein products, an indicator of oxidative stress. Rats injected with shRNA against AT1a and exposed to CIH had less FosB staining in MnPO and the rostral ventrolateral medulla after intermittent hypoxia than rats injected with the control vector that were exposed to CIH. Our results indicate AT1a receptors in the MnPO contribute to the sustained blood pressure increase to intermittent hypoxia.

Tunable broadband terahertz polarizer using graphene-metal hybrid metasurface.

We demonstrate an electrically tunable polarizer for terahertz (THz) frequency electromagnetic waves formed from a hybrid graphene-metal metasurface. Broadband (>3 THz) polarization-dependent modulation of THz transmission is demonstrated as a function of the graphene conductivity for various wire grid geometries, each tuned by gating using an overlaid ion gel. We show a strong enhancement of modulation (up to ∼17 times) compared to graphene wire grids in the frequency range of 0.2-2.5 THz upon introduction of the metallic elements. Theoretical calculations, considering both plasmonic coupling and Drude absorption, are in good agreement with our experimental findings.

Increasing the sensitivity of terahertz split ring resonator metamaterials for dielectric sensing by localized substrate etching.

We demonstrate a significant enhancement in the sensitivity of split ring resonator terahertz metamaterial dielectric sensors by the introduction of etched trenches into their inductive-capacitive gap area, both through finite element simulations and in experiments performed using terahertz time-domain spectroscopy. The enhanced sensitivity is demonstrated by observation of an increased frequency shift in response to overlaid dielectric material of thicknesses up to 18 µm deposited on to the sensor surface. We show that sensitivity to the dielectric is enhanced by a factor of up to ∼2.7 times by the incorporation of locally etched trenches with a depth of ∼3.4 µm, for example, and discuss the effect of the etching on the electrical properties of the sensors. Our experimental findings are in good agreement with simulations of the sensors obtained using finite element methods.

Detection sensitivity of laser feedback interferometry using a terahertz quantum cascade laser.

We report on the high detection sensitivity of a laser feedback interferometry scheme based on a terahertz frequency quantum cascade laser (QCL). We show that variations on the laser voltage induced by optical feedback to the laser can be resolved with the reinjection of powers as low as ∼-125 dB of the emitted power. Our measurements demonstrate a noise equivalent power of ∼1.4 pW/√Hz, although, after accounting for the reinjection losses, we estimate that this corresponds to only ∼1 fW/√Hz being coupled to the QCL active region.