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Objective: Evaluation of the effect of endothelin type A (ETA) receptor blockade on the course of volume-overload heart failure in rats with angiotensin II-dependent hypertension. Methods: Ren-2 renin transgenic rats (TGR) were used as a model of hypertension. Heart failure was induced by creating an aorto-caval fistula (ACF). Selective ETA receptor blockade was achieved by atrasentan. For comparison, other rat groups received trandolapril, an angiotensinconverting enzyme inhibitor (ACEi). Animals first underwent ACF creation and 2 weeks later the treatment with atrasentan or trandolapril, alone or combined, was applied; the follow-up period was 20 weeks. Results: Eighteen days after creating ACF, untreated TGR began to die, and none was alive by day 79. Both atrasentan and trandolapril treatment improved the survival rate, ultimately to 56% (18 of 31 animals) and 69% (22 of 32 animals), respectively. Combined ACEi and ETA receptor blockade improved the final survival rate to 52% (17 of 33 animals). The effects of the three treatment regimens on the survival rate did not significantly differ. All three treatment regimens suppressed the development of cardiac hypertrophy and lung congestion, decreased left ventricle (LV) end-diastolic volume and LV end-diastolic pressure, and improved LV systolic contractility in ACF TGR as compared with their untreated counterparts. Conclusion: The treatment with ETA receptor antagonist delays the onset of decompensation of volume-overload heart failure and improves the survival rate in hypertensive TGR with ACF-induced heart failure. However, the addition of ETA receptor blockade did not enhance the beneficial effects beyond those obtained with standard treatment with ACEi alone. Keywords: endothelin system, hypertension, Ren-2 renin transgenic rat, renin–angiotensin system, volume-overload heart failure Abbreviations: ACE, angiotensin-converting enzyme; ACF, aorto-caval fistula; ACEi, angiotensin-converting enzyme inhibitor; ANG II, angiotensin II; ANG 1–7, angiotensin-(1–7); (þdP/dt)max, maximum rates of pressure rise; (dP/dt)max, maximum rates of pressure fall; ESPVR, end-systolic pressure–volume relationship; ETA, endothelin type A; ET-1, endothelin 1; HanSD, Hannover Sprague- Dawley rats; LV, left ventricle; LVEDP, left ventricle enddiastolic pressure; LVEDV, left ventricle end-diastolic volume; PRSW, preload recruitable stroke work; RAAS, renin–angiotensin–aldosterone system; RV, right ventricle; SNS, sympathetic nervous system; TGR, Ren-2 renin transgenic rats; TPR, total peripheral resistance

The impact of bismuth incorporation into the epitaxial layer of a (Ga,Mn)As dilute ferromagnetic semiconductor on its magnetic and electromagnetic properties is studied in very thin layers of quaternary (Ga,Mn)(Bi,As) compound grown on a GaAs substrate under a compressive misfit strain. An addition of a small atomic fraction of 1% Bi atoms, substituting As atoms in the layer, predominantly enhances the spin–orbit coupling strength in its valence band. The presence of bismuth results in a small decrease in the ferromagnetic Curie temperature and a distinct increase in the coercive fields. On the other hand, the Bi incorporation into the layer strongly enhances the magnitude of negative magnetoresistance without affecting the hole concentration in the layer. The negative magnetoresistance is interpreted in terms of the suppression of weak localization in a magnetic field. Application of the weak-localization theory for two-dimensional ferromagnets by Dugaev et al. to the experimental magnetoresistance results indicates that the decrease in spin–orbit scattering length accounts for the enhanced magnetoresistance in (Ga,Mn)(Bi,As).

The lattice mismatch between interesting 2D materials and commonly available 3D substrates is one of the obstacles in the epitaxial growth of monolithic 2D/3D heterostructures, but a number of 2D materials have not yet been considered for epitaxy. Here we present the first molecular beam epitaxy growth of NiTe$_{2}$ 2D transition metal dichalcogenide. Importantly, the growth is realized on a nearly lattice matched GaAs(111)B substrate. Structural properties of the grown layers are investigated by electron diffraction, X-ray diffraction, and scanning tunnelling microscopy. Surface coverage and atomic scale order is evidenced by images obtained with atomic force, scanning electron, and transmission electron microscopy. Basic transport properties were measured confirming that NiTe$_{2}$ layers are metallic, with the Hall concentration of $10^{20}$cm$^{-3}$ to $10^{23}$cm$^{-3}$, depending on the growth conditions.

Thin crystalline layers of TaAs Weyl semimetal (9 and 18 nm thick) are grown by molecular beam epitaxy on GaAs(001) substrates. The (001) planes of the tetragonal TaAs lattice are parallel to the GaAs(001) substrate, but the corresponding in-plane crystallographic directions of the substrate and the layer are rotated by 45{\deg}. In spite of a substantial lattice mismatch (about 19%) between GaAs(001) substrate and TaAs epilayer no misfit dislocations are observed at the GaAs(001)/TaAs(001) interface. Only stacking fault defects in TaAs are detected with transmission electron microscopy. Thorough X-ray diffraction measurements and analysis of the in-situ reflection high energy electron diffraction images indicates that TaAs layers are fully relaxed already at the initial deposition stage. Atomic force microscopy imaging reveals the columnar structure of the layers, with lateral (parallel to the layer surface) columns about 20 nm wide and 200 nm long. Both X-ray diffraction and transmission electron microscopy measurements indicate that the columns share the same orientation and crystalline structure., Comment: 23 pages, 6 figures

The intrarenal dopamine system has been thoroughly investigated at all levels, especially its role in salt-dependent and other forms of hypertension. However, the evidence regarding dopamine's tonic influence on renal tubular transport of sodium remains equivocal. We reinvestigated its tonic influence on sodium excretion and systemic and renal haemodynamics. Early effects of dopamine D1 receptor blockade using 90-min Schering 23390 (SCH) infusion were examined in anaesthetized rats on 7 days' high salt diet (HS), early uninephrectomized rats on 14 days' HS diet, drinking 1% saline (HS/UNX), and in spontaneously hypertensive rats (SHR). In the HS group (baseline BP ~133 mm Hg) renal intracortical SCH promptly decreased sodium, water and total solute excretion (UNa V, V, Uosm V), with significant difference from the solvent-infused group. BP and renal artery blood flow (RBF, Transonic probe) did not change. In HS/UNX model (baseline BP ~150 mm Hg), characterized by hypertrophy of the remaining kidney, the excretion parameters only tended to decrease whereas SCH induced an ~20% fall in RBF. In SHR (BP ~180 mm Hg), UNa V and V tended to increase in solvent-infused rats; this increasing tendency was abolished by SCH infusion. During experiments the renal vascular resistance increased significantly in SCH- and solvent-infused SHR. Despite some contradictory findings regarding the genuine tonic control of renal excretion by intrarenal dopamine, our results clearly support such role in rats on HS diet and in SHR, the model resembling human essential hypertension. The observations strengthen the experimental basis and the rationale for targeting the intrarenal dopamine system in attempts to combat arterial hypertension.

Background: The coincidence of congestive heart failure (CHF) and chronic kidney disease (CKD) results in poor survival rate. The aim of the study was to examine if renal denervation (RDN) would improve the survival rate in CHF induced by creation of aorto-caval fistula (ACF).Methods: Fawn-hooded hypertensive rats (FHH), a genetic model of spontaneous hypertension associated with CKD development, were used. Fawn-hooded low-pressure rats (FHL), without CKD, served as controls. RDN was performed 4 weeks after creation of ACF and the follow-up period was 10 weeks.Results: We found that intact (non-denervated) ACF FHH exhibited survival rate of 58.8% (20 out of 34 rats), significantly lower than in intact ACF FHL (81.3%, 26/32 rats). In intact ACF FHL albuminuria remained stable throughout the study, whereas in ACF FHH it increased significantly, up to a level 40-fold higher than the basal values. ACF FHL did not show increases in renal glomerular and tubulointerstitial injury as compared with FHL, while ACF FHH exhibited marked increases in kidney injury as compared with FHH. RDN did not improve the survival rate in either ACF FHL or ACF FHH and did not alter the course of albuminuria in ACF FHL. RDN attenuated the albuminuria, but did not reduce the kidney injury in ACF FHH.Conclusions: Our present results support the notion that even modest CKD increases CHF-related mortality. RDN did not attenuate CHF-dependent mortality in ACF FHH, it delayed the progressive rise in albuminuria, but it did not reduce the degree of kidney injury.

Earlier evidence from studies of rat hypertension models undermines the widespread view that the rate of renal medullary blood flow (MBF) is critical in control of arterial pressure (MAP). Here, we examined the role of MBF in rats that were normotensive, with modest short-lasting pressure elevation, or with overt established hypertension. The groups studied were anaesthetised Sprague-Dawley rats: (1) normotensive, (2) with acute i.v. norepinephrine-induced MAP elevation, and (3) with hypertension induced by unilateral nephrectomy followed by administration of deoxycorticosterone-acetate (DOCA) and 1% NaCl drinking fluid for 3 weeks. MBF was measured (laser-Doppler probe) and selectively increased using 4-h renal medullary infusion of bradykinin. MAP, renal excretion parameters and post-experiment medullary tissue osmolality and sodium concentration were determined. In the three experimental groups, baseline MAP was 117, 151 and 171 mmHg, respectively. Intramedullary bradykinin increased MBF by 45%, 65% and 70%, respectively, but this was not associated with a change in MAP. In normotensive rats a significant decrease in medullary tissue sodium was seen. The intramedullary bradykinin specifically increased renal excretion of water, sodium and total solutes in norepinephrine-treated rats but not in the two other groups. As previously shown in models of rat hypertension, in the normotensive rats and those with acute mild pressure elevation (resembling labile borderline human hypertension), 4-h renal medullary hyperperfusion failed to decrease MAP. Nor did it decrease in DOCA-salt model mimicking low-renin human hypertension. Evidently, within the 4-h observation, medullary perfusion was not a critical determinant of MAP in normotensive and hypertensive rats.

Objective: We examined if renal denervation (RDN) attenuates the progression of aortocaval fistula (ACF)-induced heart failure or improves renal hemodynamics in Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension. Methods: Bilateral RDN was performed 1 week after creation of ACF. The animals studied were ACF TGR and sham-operated controls, and both groups were subjected to RDN or sham denervation. In separate groups, renal artery blood flow (RBF) responses were determined to intrarenal ANG II (2 and 8 ng), norepinephrine (NE) (20 and 40 ng) and acetylcholine (Ach) (10 and 40 ng) 3 weeks after ACF creation. Results: In nondenervated ACF TGR, the final survival rate was 10 versus 50% in RDN rats. RBF was significantly lower in ACF TGR than in sham-operated TGR (6.2 ± 0.3 vs. 9.7 ± 0.5 mL min−1 g−1, p < 0.05), the levels unaffected by RDN. Both doses of ANG II decreased RBF more in ACF TGR than in sham-operated TGR (−19 ± 3 vs. −9 ± 2% and −47 ± 3 vs. −22 ± 2%, p < 0.05 in both cases). RDN did not alter RBF responses to the lower dose, but increased it to the higher dose of ANG II in sham-operated as well as in ACF TGR. NE comparably decreased RBF in ACF TGR and sham-operated TGR, and RDN increased RBF responsiveness. Intrarenal Ach increased RBF significantly more in ACF TGR than in sham-operated TGR (29 ± 3 vs. 17 ± 3%, p < 0.05), the changes unaffected by RDN. ACF creation induced marked bilateral cardiac hypertrophy and lung congestion, both attenuated by RDN. In sham-operated but not in ACF TGR, RDN significantly decreased mean arterial pressure. Conclusion: The results show that RDN significantly improved survival rate in ACF TGR; however, this beneficial effect was not associated with improvement of reduced RBF or with attenuation of exaggerated renal vascular responsiveness to ANG II.

Current data indicate that heart failure (HF) is associated with inflammation and microvascular dysfunction and remodeling. These mechanisms could be involved in HF development and progression, especially in HF with preserved ejection fraction (HFpEF). We aimed to compare structural changes in retinal arterioles and carotid arteries between HF patients and patients without heart failure. This preliminary, retrospective, case-control study included 28 participants (14 patients with HFpEF and 14 age- and sex-matched healthy controls). Carotid intima-media thickness to lumen ratio (cIMTLR) was assessed using B-mode ultrasonography. Retinal arterioles wall- to-lumen ratio (rWLR) was assessed by adaptive optics camera rtx1. The HF patients had higher IMTLR (Δmedian [HFpEF–control group] 0.07, p = 0.01) and eWLR (Δmedian 0.03, p = 0.001) in comparison to patients without HF. In the whole study group, rWLR correlated significantly with IMTLR (r = 0.739, p = 0.001). Prevalence of arterial hypertension was similar in both groups, however, patients with HF had a significantly lower office, central and 24-h ambulatory blood pressure (systolic Δmedian −21 to −18 mmHg; diastolic Δmedian −23 to −10 mmHg). Our data suggests gradual and simultaneous progression of vascular remodeling in both retinal arterioles and carotid arteries in HFpEF patients. This process could be a marker of HF development. Significantly lower blood pressure values in HF group may indicate that vascular remodeling could be independent of BP control. Nevertheless, further and larger prospective studies allowing to reduce the impact of confounding and address temporality are warranted.

In the context of the ongoing debate on the mechanism of blood pressure (BP) regulation and pathophysiology of arterial hypertension ("renocentric" vs "neural" concepts), attention is focused on the putative regulatory role of changes in renal medullary blood flow (MBF). Experimental evidence is analysed with regard to the question whether an elevation of BP and renal perfusion pressure (RPP) is likely to increase MBF due to its impaired autoregulation. It is concluded that such increases have been clearly documented only in rats with extracellular fluid volume expansion. A possible translation of this finding to BP regulation in health and hypertension in humans may only be a matter of speculation. Within the "renocentric" theory, the key event leading to restoration of initial BP level is pressure natriuresis. Its relation to elevation of renal interstitial hydrostatic pressure and to the phenomenon of "wash-out" of renal medullary solutes by increasing MBF is discussed. We also assessed the validity of data supporting the putative mechanism of short-term restoration of elevated BP owing to the release of a vasodilator lipid (medullipin) by the medulla. The structure of the proposed medullary lipid is still undefined, and there is no sound evidence on its mediatory role in lowering elevated BP level. In conclusion, MBF change can hardly be regarded as a crucial event in the regulation of BP: it can be involved in the control of sodium excretion and BP only in some circumstances, although its contributory role cannot be excluded.

The purpose of this review was to discuss the role of sodium and inflammation in the pathophysiology of hypertension and the observed different hemodynamic effects of drugs. The Pathway-2 study revealed that similar reductions in vascular resistance after spironolactone and doxazosin resulted in opposite effects on sodium balance, water retention, and hemodynamic parameters. These and other clinical findings were bridged to recent experimental and physiological data. Tissue sodium accumulation in salt-sensitive individuals due to endothelial glycocalyx dysfunction causes macrophage infiltration, vascular inflammation, and local changes in angiotensin-2 and aldosterone concentrations. This inflammatory cascade leads to factor XII-related coagulation disorders with neutrophil extracellular trap formation (NETosis). This model of sodium-induced microcirculation impairment was used to explain the differences in central hemodynamic parameters after spironolactone or doxazosin treatment in resistant hypertension. Hypertension treatment by induced sodium removal or reduced sodium intake should reduce endothelial glycocalyx dysfunction, inflammation, NETosis, and coagulation disorders, leading to improved vascular health and cardiac diastolic function.

Thin layers of transition metal dichalcogenides have been intensively studied over the last few years due to their novel physical phenomena and potential applications. One of the biggest problems in laboratory handling and moving on to application-ready devices lies in the high sensitivity of their physicochemical properties to ambient conditions. We demonstrate that novel, in situ capping with an ultra-thin, aluminum film efficiently protects thin MoTe2 layers stabilizing their electronic transport properties after exposure to ambient conditions. The experiments have been performed on bilayers of 2H-MoTe2 grown by molecular beam epitaxy on large area GaAs(111)B substrates. The crystal structure, surface morphology and thickness of the deposited MoTe2 layers have been precisely controlled in situ with a reflection high energy electron diffraction system. As evidenced by high resolution transmission electron microscopy, MoTe2 films exhibit perfect arrangement in the 2H phase and the epitaxial relation to the GaAs(111)B substrates. After the growth, the samples were in situ capped with a thin (3 nm) film of aluminum, which oxidizes after exposure to ambient conditions. This oxide serves as a protective layer to the underlying MoTe2. Resistivity measurements of the MoTe2 layers with and without the cap, exposed to low vacuum, nitrogen and air, revealed a huge difference in their stability. The significant rise of resistance is observed for the unprotected sample while the resistance of the protected one is constant. Wide range temperature resistivity studies showed that charge transport in MoTe2 is realized by hopping with an anomalous hopping exponent of x ≃ 0.66, reported also previously for ultra-thin, metallic layers.

Incorporation of Bi into GaAs-(Ga,Al)As-Ga(As,Bi) core-shell nanowires grown by molecular beam epitaxy is studied with transmission electron microscopy. Nanowires are grown on GaAs(111)B substrates with Au-droplet assisted mode. Bi-doped shells are grown at low temperature (300 {\deg}C) with a close to stoichiometric Ga/As flux ratio. At low Bi fluxes, the Ga(As,Bi) shells are smooth, with Bi completely incorporated into the shells. Higher Bi fluxes (Bi/As flux ratio ~ 4%) led to partial segregation of Bi as droplets on the nanowires sidewalls, preferentially located at the nanowire segments with wurtzite structure. We demonstrate that such Bi droplets on the sidewalls act as catalysts for the growth of branches perpendicular to the GaAs trunks. Due to the tunability between zinc-blende and wurtzite polytypes by changing the nanowire growth conditions, this effect enables fabrication of branched nanowire architectures with branches generated from selected (wurtzite) nanowire segments., Comment: 41 pages, 14 figures

Pulsed current-induced magnetization reversal is investigated in the layer of (Ga,Mn)(Bi,As) dilute ferromagnetic semiconductor (DFS) epitaxially grown under tensile misfit strain causing perpendicular magnetic anisotropy in the layer. The magnetization reversal, recorded through measurements of the anomalous Hall effect, appearing under assistance of a static magnetic field parallel to the current, is interpreted in terms of the spin-orbit torque mechanism. Our results demonstrate that an addition of a small fraction of heavy Bi atoms, substituting As atoms in the prototype DFS (Ga,Mn)As and increasing the strength of spin-orbit coupling in the DFS valence band, significantly enhances the efficiency of current-induced magnetization reversal thus reducing considerably the threshold current density necessary for the reversal. Our findings are of technological importance for applications to spin-orbit torque-driven nonvolatile memory and logic elements., Comment: 8 pages, 5 figures

Challenges and opportunities arising from molecular beam epitaxial growth of topological crystalline insulator heterostructures composed of a rock-salt SnTe(001) layer of varying thickness (from 80 nm to 1000 nm) and a zinc blende 4 mu m thick CdTe(001) buffer layer grown on a commercial GaAs(001) substrate with 2 degrees off-cut toward the [100] direction were studied with a focus on crystal lattice strain, unit cell symmetry breaking and surface quality. The results indicate that the CdTe buffer is almost fully relaxed whereas in SnTe layers slight anisotropic relaxation is observed that varies from 86.2% to 98.3% with the layer thickness increasing. The relaxation process involves formation of misfit dislocations, mainly of Lomer-type (consisting of two associated 60 degrees dislocations), both at CdTe/GaAs and SnTe/CdTe interfaces. Azimuthal spatial distribution of defects is anisotropic due to a disparity of 60 degrees dislocation mobility toward orthogonal [-110] and [110] crystallographic directions. This results in a monoclinic distortion of the SnTe unit cell, as observed especially in the layers grown without additional Te molecular flux. A reflections selection method is proposed to measure such crystal deformations. Qualitatively new morphology of the SnTe surface of a reduced symmetry with nanoripple-like structures oriented close to the 100 (or, rarely, to 120) crystallographic in-plane direction is observed. The possible mechanism of their formation is dislocation-driven while their extended shape and predominant crystalline orientation may be influenced by the anisotropy of defect azimuthal distribution. Due to the magnitude of measured lattice strain (similar to 10(-3)) the monoclinic distortion in SnTe(001) layers is expected to be large enough to affect their physical properties, e.g., offering the way of controlling the crystal-symmetry-protected surface states (deformation-induced opening of the energy gap in the spectrum of metallic topological surface states). Thus, it may serve as an additional degree of freedom in designing topological spintronic devices.

Association of congestive heart failure (CHF) and chronic kidney disease (CKD) worsens the patient's prognosis and results in poor survival rate. The aim of this study was to examine if addition of endothelin type A (ETCKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of aorto-caval fistula (ACF). The follow-up was 24 weeks after the first intervention (5/6 NX). The treatment regimens were initiated 6 weeks after 5/6 NX and 2 weeks after ACF creation.The final survival in untreated group was 15%. The treatment with ETOur results show that treatment with ET

We found previously that intravenous kynurenic acid (KYNA), a native broad spectrum glutamate antagonist, increases renal blood flow and induces natriuresis in anesthetized spontaneously hypertensive rats (SHR). Since such changes may affect systemic circulation and can potentially find therapeutic application, in this study we examined long term influence of orally administered KYNA on systemic and renal hemodynamics and renal excretion in conscious SHR. KYNA was administered in drinking water at a dose of 25 mg/kg/day for 3 weeks. Heart rate (HR), systolic (SBP), and mean arterial pressure (MAP) were measured through telemetry. The records were taken at the beginning of the study (control, day 0), and then on day 7, 14, and 21 of treatment. Diuresis (V), total solute excretion (UosmV), and sodium excretion (UNaV) were determined on days 0, 7, and 14. KYNA consistently decreased HR, from 319 ± 8 to 291 ± 5, 299 ± 9 and 284 ± 6 beats/min on day 7, 14, and 21, respectively, (− 9, − 6, and − 11%; p

Introduction: Previous studies in Ren-2 transgenic hypertensive rats (TGR) after 5/6 renal ablation (5/6 NX) have shown that besides pharmacological blockade of the renin-angiotensin system (RAS) also increasing kidney tissue epoxyeicosatrienoic acids (EET) levels by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for degradation of EETs, and endothelin type A (ETA) receptor blockade retards chronic kidney disease (CKD) progression. This prompted us to evaluate if this progression will be alleviated by the addition of sEH inhibitor and ETA receptor antagonist to the standard complex blockade of RAS (angiotensin-converting enzyme inhibitor plus angiotensin II type 1 receptor blocker) in rats with established CKD. Methods: The treatment regimens were initiated 6 weeks after 5/6 NX in TGR, and the follow-up period was 60 weeks. Results: The addition of sEH inhibition to RAS blockade improved survival rate, further reduced albuminuria and renal glomerular and kidney tubulointerstitial injury, and attenuated the decline in creatinine clearance – all this as compared with 5/6 NX TGR treated with RAS blockade alone. Addition of ETA receptor antagonist to the combined RAS and sEH blockade not only offered no additional renoprotection but, surprisingly, also abolished the beneficial effects of adding sEH inhibitor to the RAS blockade. Conclusion: These data indicate that pharmacological strategies that combine the blockade of RAS and sEH could be a novel tool to combat the progression of CKD. Any attempts to further extend this therapeutic regimen should be made with extreme caution.

We found recently that in Ren-2 transgenic hypertensive rats (TGR) addition of soluble epoxide hydrolase inhibitor (sEHi) to treatment with angiotensin-converting enzyme inhibitor (ACEi), surprisingly, increased the mortality due to heart failure (HF) induced by creation of the aorto-caval fistula (ACF). Since TGR exhibit sex-related differences in mortality, we examined here if such differentiation exists also in the response to the treatment with ACEi (trandolapril), alone or combined with sEHi [cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid, (c-AUCB)]. ACEi improved survival in males to 74 % (vs. 0 %) and in females to 65 % (vs. 32 %). ACEi and sEHi combined also improved the survival in male ACF TGR, however, it was significantly less (38 %) than after ACEi alone. In contrast, in females the combined treatment significantly improved the final survival rate (84 %). There were no significant sex-linked differences in survival rate in untreated or treated normotensive Hannover Sprague-Dawley rats. In conclusion, in HF patients with co-existing hypertension and RAS hyperactivity, the sex may co-determine the rate of HF progression, and can influence the effectiveness of the therapeutic measures applied. Therefore, in the relevant pre-clinical studies the sex-linked differences should be seriously considered. Our data indicate that TGR might be an optimal model for such studies.

The aim of the present study was to perform kidney messenger ribonucleic acid (mRNA) analysis in normotensive, Hannover Sprague–Dawley (HanSD) rats and hypertensive, Ren-2 renin transgenic rats (TGR) after doxorubicin-induced heart failure (HF) with specific focus on genes that are implicated in the pathophysiology of HF-associated cardiorenal syndrome. We found that in both strains renin and angiotensin-converting enzyme mRNA expressions were upregulated indicating that the vasoconstrictor axis of the renin–angiotensin system was activated. We found that pre-proendothelin-1, endothelin-converting enzyme type 1 and endothelin type A receptor mRNA expressions were upregulated in HanSD rats, but not in TGR, suggesting the activation of endothelin system in HanSD rats, but not in TGR. We found that mRNA expression of cytochrome P-450 subfamily 2C23 was downregulated in TGR and not in HanSD rats, suggesting the deficiency in the intrarenal cytochrome P450-dependent pathway of arachidonic acid metabolism in TGR. These results should be the basis for future studies evaluating the pathophysiology of cardiorenal syndrome secondary to chemotherapy-induced HF in order to potentially develop new therapeutic approaches.

Purpose of Review To analyze the impact of sodium retention states on the course of COVID-19 and propose possible interventions to curb disease progression. Recent Findings Numerous data confirm a positive association of non-communicable diseases, aging, and other sodium-retaining states, including iatrogenic ones, with more severe sometimes fatal clinical course of COVID-19. Reasons for this effect could include increased angiotensin signaling via the AT1R receptor. The endothelial glycocalyx also plays an important role in infection, leading to a vicious cycle of inflammation and tissue sodium retention when damaged. RAS inhibitors may help restore glycocalyx function and prevent severe organ damage. Anticoagulants, especially heparin, may also have therapeutic applications due to antithrombotic, anti-inflammatory, glycocalyx-repairing, and antialdosteronic properties. The ambiguous influence of some diuretics on sodium balance was also discussed. Summary Abnormal sodium storage and increased angiotensin-converting enzyme activity are related to the severity of COVID-19. Inducing sodium removal and reducing intake might improve outcomes.

Here we report on detailed studies of the magnetic properties of the wurtzite (Ga,Mn)As cylindrical shells. Ga$_{0.94}$Mn$_{0.06}$As shells have been grown by molecular beam epitaxy at low temperature as a part of multishell cylinders overgrown on wurtzite (Ga,In)As nanowires cores, synthesized on GaAs (111)B substrates. Our studies clearly indicate the presence of a low temperature ferromagnetic coupling, which despite a reasonably high Mn contents of 6\% is limited only to below 30~K. A set of dedicated measurements shows that despite a high structural quality of the material the magnetic order has a granular form, which gives rise to the dynamical slow-down characteristic to blocked superparamagnets. The lack of the long range order has been assigned to a very low hole density, caused primarily by numerous compensation donors, arsenic antisites, formed in the material due to a specific geometry of the growth of the shells on the nanowire template. The associated electrostatic disorder has formed a patchwork of spontaneously magnetized (macrospin) and nonmagnetic (paramagnetic) volumes in the material. Using high field results it has been evaluated that the total volume taken by the macrospins constitute about 2/3 of the volume of the (Ga,Mn)As whereas in the remaining 1/3 only paramagnetic Mn ions reside. By establishing the number of the uncoupled ions the two contributions were separated. The Arrott plot method applied to the superparamagnetic part yielded the first experimental assessment of the magnitude of the spin-spin coupling temperature within the macrospins in (Ga,Mn)As, $T_{\mathrm{C}}=28$~K. In a broader view our results constitute an important contribution to the still ongoing dispute on the true and the dominant form(s) of the magnetism in this model dilute ferromagnetic semiconductor., 23 pages, 7 figures

Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone.

Physical review / B 103(7), 075107 (1-13) (2021). doi:10.1103/PhysRevB.103.075107, Diluted ferromagnetic semiconductors combining ferromagnetic and semiconducting properties in one material provide numerous new functionalities, attractive for basic studies and potentially useful for novel device applications. The tailoring of the electronic structure in analogy to conventional semiconductors has yet to be explored. Here, we demonstrate the conservation of broken inversion symmetry and band structure tailoring for high-quality molecular-beam-epitaxy-grown (In,Ga,Mn)As films with 3% In plus 2.5% or 5.6% Mn using hard-x-ray photoelectron diffraction (hXPD) and momentum microscopy. Photon energies of 3–5 keV ensure that the results are not corrupted by surface effects, which are known to be strong in semiconductors. The missing inversion center of the GaAs host lattice leads to fingerprint-like hXPD signatures of As and Ga sites. For both concentrations, Mn predominantly occupies Ga substitutional sites. Momentum microscopy reveals a shift of the chemical potential with increasing Mn doping and a highly dispersing band, crossing the Fermi level for high Mn concentration. The Mn doping induces a pronounced modification of the spin-orbit split-off band., Published by Inst., Woodbury, NY

Thin layers of transition metal dichalcogenides have been intensively studied over the last few years due to their novel physical phenomena and potential applications. One of the biggest problems in laboratory handling and moving on to application-ready devices lies in the high sensitivity of their physicochemical properties to ambient conditions. We demonstrate that novel, in situ capping with an ultra-thin, aluminum film efficiently protects thin MoTe2 layers stabilizing their electronic transport properties after exposure to ambient conditions. The experiments have been performed on bilayers of 2H-MoTe2 grown by molecular beam epitaxy on large area GaAs(111)B substrates. The crystal structure, surface morphology and thickness of the deposited MoTe2 layers have been precisely controlled in situ with a reflection high energy electron diffraction system. As evidenced by high resolution transmission electron microscopy, MoTe2 films exhibit perfect arrangement in the 2H phase and the epitaxial relation to the GaAs(111)B substrates. After the growth, the samples were in situ capped with a thin (3 nm) film of aluminum, which oxidizes after exposure to ambient conditions. This oxide serves as a protective layer to the underlying MoTe2. Resistivity measurements of the MoTe2 layers with and without the cap, exposed to low vacuum, nitrogen and air, revealed a huge difference in their stability. The significant rise of resistance is observed for the unprotected sample while the resistance of the protected one is constant. Wide range temperature resistivity studies showed that charge transport in MoTe2 is realized by hopping with an anomalous hopping exponent of x ≃ 0.66, reported also previously for ultra-thin, metallic layers.

OBJECTIVES The global morbidity and mortality related to hypertension and associated disorders increases continuously and novel therapeutic strategies are still in high demand. Increasing evidence suggests the important role in blood pressure regulation of cytochrome P-450-dependent metabolites of arachidonic acid. Epoxyeicosatrienoic acids (EETs) induce vasodilation and natriuresis, and have renoprotective and anti-inflammatory properties. 20-HETE is an arachidonic acid metabolite with both prohypertensive and antihypertensive activities. To explore the pathophysiological role of arachidonic acid metabolites in more detail, we examined the antihypertensive efficiency of EET-A, a stable analog of 14,15-EET, and of AAA, a novel antagonist of the 20-HETE receptors. METHODS Male spontaneously hypertensive rats (SHR) were treated for 5 weeks with EET-A, AAA or the combination; age-matched untreated SHR and normotensive Wistar-Kyoto rats served as controls. EET-A and AAA were administered in drinking water at 10 mg/kg/day each. SBP was measured by telemetry and urine, blood, and tissue samples were collected for relevant analyses. RESULTS EET-A or AAA given alone had no significant effect on SHR blood pressure. In contrast, combined treatment with AAA and EET-A was significantly antihypertensive, causing a decrease in SBP from 180 ± 3 to 160 ± 5 mmHg (P

The adenosine (Ado) system may participate in regulation of kidney function in diabetes mellitus (DM), therefore we explored its role and interrelation with NO in the control of renal circulation and excretion in normoglycemic (NG) and streptozotocin-diabetic (DM) rats. Effects of theophylline (Theo), a non-selective Ado receptor antagonist, were examined in anaesthetized NG or in streptozotocin induced diabetic (DM) rats, untreated or after blockade of NO synthesis with l-NAME. We measured arterial blood pressure (MABP), whole kidney blood flow and renal regional flows: cortical and outer- and inner-medullary (IMBF), determined as laser-Doppler fluxes. Renal excretion of water, total solutes and sodium and in situ renal tissue NO signal (selective electrodes) were also determined. Theo experiments disclosed minor baseline vasoconstrictor and vasodilator tone in the kidney of NG and DM rats, respectively. NO blockade increased baseline MABP and decreased renal haemodynamics, similarly in NG and DM rats, indicating comparable vasodilator influence of NO in the two groups. Unexpectedly, in all rats with intact NO synthesis, Ado receptor blockade increased kidney tissue NO. In NO-deficient NG and DM rats, Ado receptor blockade induced comparable renal vasodilatation, suggesting similar vasoconstrictor influence of the Ado system. However, DM rats showed an unexplained association of decreased MABP and IMBF and increased NO signal. Higher baseline renal excretion in DM rats indicated inhibition of renal tubular reabsorption due to the prevalence of natriuretic A2 over antinatriuretic A1 receptors. In conclusion, the experiments provided new insights in functional interrelation of adenosine and NO in normoglycaemia and streptozotocin-diabetes.

We critically discuss various experimental methods to determine Curie temperature T C of (Ga,Mn)As thin layers or other conducting magnetic materials by means of electric charge transport measurements. They all base on the influence of sample magnetization on the magnetoresistivity tensor ρ and are an alternative to the method based upon an analysis of the temperature derivative of the sample resistance (Novak et al., 2008). These methods can be applied even when standard SQUID magnetometers are difficult or impossible to use – for example for extremely small samples or in the case of experiments performed at very specific physical conditions, e.g. at high hydrostatic pressure inside the clamp cell. We show that the use of the so called Arrott plot prepared with the use of high magnetic field isotherms ρ xx ( H 0 ) , ρ xy ( H 0 ) ( H 0 – external magnetic field) may lead to substantial (of the order of 10 K) divergence of the obtained T C values depending on the assumptions which are necessary to make in this case and depending on the direction of a magnetic anisotropy easy axis. We also propose a number of ways how to obtain, basing on low magnetic field isotherms ρ xx ( H 0 ) , ρ xy ( H 0 ) , clear and characteristic features which are closely related to the ferromagnetic–paramagnetic phase transition.

• The Ga 1-x Mn x As/InGaAs layer exhibits a strong sensitivity to the magnetic field and temperature.

Background/Aims: Reduction of renal blood flow (RBF) is commonly thought to be a causative factor of renal dysfunction in congestive heart failure (CHF), but the exact mechanism of the renal hypoperfusion is not clear. Apart from the activation of neurohormonal systems controlling intrarenal vascular tone, the cause might be altered reactivity of the renal vasculature to endogenous vasoactive agents. Methods: To evaluate the role of this mechanism, we assessed by an ultrasonic transient-time flow probe maximum RBF responses to renal artery infusion of angiotensin II (ANG II), norepinephrine (NE) and acetylcholine (Ach) in healthy male rats and animals with compensated and decompensated CHF. CHF was induced by volume overload achieved by the creation of the aorto-caval fistula (ACF) in Hannover Sprague-Dawley rats. Results: Maximum responses in RBF to ANG II were similar in rats studied five weeks (compensated phase) and 20 weeks (decompensated phase) after ACF creation when compared to sham-operated rats. On the other hand, NE elicited larger maximum decreases in RBF in rats with CHF (five and 20 weeks post-ACF) than in sham-operated controls. We observed greater maximum vasodilatory responses to Ach only in rats with a compensated stage of CHF (five weeks post-ACF). Conclusion: Greater renal vasoconstrictor responsiveness to ANG II or reduced renal vasodilatation in response to Ach do not play a decisive role in the development of renal dysfunction in ACF rats with compensated and decompensated CHF. On the other hand, exaggerated renal vascular responsiveness to NE may be here a contributing causative factor, active in either CHF phase.