Excess dietary salt is a major cause of hypertension. Nevertheless, the specific mechanisms by which salt increases arterial constriction and peripheral vascular resistance, and thereby raises blood ...pressure (BP), are poorly understood. Here we summarize recent evidence that defines specific molecular links between Na(+) and the elevated vascular resistance that directly produces high BP. In this new paradigm, high dietary salt raises cerebrospinal fluid Na(+). This leads, via the Na(+)-sensing circumventricular organs of the brain, to increased sympathetic nerve activity (SNA), a major trigger of vasoconstriction. Plasma levels of endogenous ouabain (EO), the Na(+) pump ligand, also become elevated. Remarkably, high cerebrospinal fluid Na(+)-evoked, locally secreted (hypothalamic) EO participates in a pathway that mediates the sustained increase in SNA. This hypothalamic signaling chain includes aldosterone, epithelial Na(+) channels, EO, ouabain-sensitive α(2) Na(+) pumps, and angiotensin II (ANG II). The EO increases (e.g.) hypothalamic ANG-II type-1 receptor and NADPH oxidase and decreases neuronal nitric oxide synthase protein expression. The aldosterone-epithelial Na(+) channel-EO-α(2) Na(+) pump-ANG-II pathway modulates the activity of brain cardiovascular control centers that regulate the BP set point and induce sustained changes in SNA. In the periphery, the EO secreted by the adrenal cortex directly enhances vasoconstriction via an EO-α(2) Na(+) pump-Na(+)/Ca(2+) exchanger-Ca(2+) signaling pathway. Circulating EO also activates an EO-α(2) Na(+) pump-Src kinase signaling cascade. This increases the expression of the Na(+)/Ca(2+) exchanger-transient receptor potential cation channel Ca(2+) signaling pathway in arterial smooth muscle but decreases the expression of endothelial vasodilator mechanisms. Additionally, EO is a growth factor and may directly participate in the arterial structural remodeling and lumen narrowing that is frequently observed in established hypertension. These several central and peripheral mechanisms are coordinated, in part by EO, to effect and maintain the salt-induced elevation of BP.
The meaning of the enigmatic verse of Acts 15:21, not to mention the issues around the preceding Apostolic Decree (vv. 19–20), has largely been researched individually and historical-critically. By ...contrast, in this study I explicate the meaning of the verse within the broader scope of James’s speech by attending to the Jewish spatiality on Luke’s narrative-ideological plane. The Lukan James’s speech tightly combines intertextual elements that bear on significant Jewish spatiality, namely, the restored tent of David (v. 16) within the quotation of Amos 9:11–12, the alluded-to holy land (v. 20) drawn from Lev 17–18 as the background of the decree, and the Jewish synagogues in every city (v. 21) as the background of James’s final invocation of Moses. From this perspective, I propose that v. 21 is part of the Lukan narrative-ideological portrait that reconfigures the holy land’s purity concern via the eschatological presence of the restored Davidic tent, making it relevant to the larger Greco-Roman world in accordance with the continuing monotheistic cultic sanctity.
Arterial smooth muscle Na
/Ca
exchanger-1 (SM-NCX1) promotes vasoconstriction or vasodilation by mediating, respectively, Ca
influx or efflux. In vivo, SM-NCX1 mediates net Ca
influx to help maintain ...myogenic tone (MT) and neuronally activated constriction. SM-NCX1-TG (overexpressing transgenic) mice have increased MT and mean blood pressure (MBP; +13.5 mmHg); SM-NCX1-KO (knockout) mice have reduced MT and MBP (-11.1 mmHg). Endothelium-dependent vasodilation (EDV) is often impaired in hypertension. We tested whether genetically engineered SM-NCX1 expression and consequent BP changes similarly alter EDV. Isolated, pressurized mesenteric resistance arteries with MT from SM-NCX1-TG and conditional SM-NCX1-KO mice, and femoral arteries in vivo from TG mice were studied. Acetylcholine (ACh)-dilated TG arteries with MT slightly more than control or KO arteries, implying that SM-NCX1 overexpression does not impair EDV. In preconstricted KO, but not TG mouse arteries, however, ACh- and bradykinin-triggered vasodilation was markedly attenuated. To circumvent the endothelium, phenylephrine-constricted resistance arteries were tested with Na-nitroprusside SNP; nitric oxide (NO) donor and cGMP. This endothelium-independent vasodilation was augmented in TG but attenuated in KO arteries that lack NCX1-mediated Ca
clearance. Baseline cytosolic Ca
(Ca
) was elevated in TG femoral arteries in vivo, supporting the high BP; furthermore, SNP-triggered Ca
decline and vasodilation were augmented as NO and cGMP promote myocyte polarization thereby enhancing NCX1-mediated Ca
efflux. The TG mouse data indicate that BP elevation does not attenuate endothelium-dependent vasodilation. Thus, in essential hypertension and many models the endothelial impairment that supports the hypertension apparently is not triggered by BP elevation but by extravascular mechanisms.
Endothelium-dependent, ACh-induced vasodilation (EDV) is attenuated, and arterial myocyte Na
/Ca
exchangers (NCX1) are upregulated in many forms of hypertension. Surprisingly, mildly hypertensive smooth muscle-specific (SM)-NCX1 transgenic mice exhibited modestly enhanced EDV and augmented endothelium-independent vasodilation (EIV). Conversely, mildly hypotensive SM-NCX1-knockout mice had greatly attenuated EIV. These adaptations help compensate for NCX1 expression-induced alterations in cytosolic Ca
and blood pressure (BP) and belie the view that elevated BP, itself, causes the endothelial dysregulation in hypertension.
Myocardial ischemia/reperfusion (I/R) induces inflammatory response that may lead to remote vascular injury. Vagal nerve elicits the cholinergic anti-inflammatory pathway by activating α7 nicotinic ...acetylcholine receptors (α7nAChR). Nevertheless, the role of vagal nerve-mediated anti-inflammatory pathway in the vasculature has not been studied previously. Therefore, we aimed to clarify the potential role of vagal stimulation (VNS) in regulating remote vascular injury after myocardial I/R. Adult male Sprague–Dawley rats were subjected to VNS starting 15 min prior to ischemia until the end of reperfusion. VNS not only reduced infarct size and improved cardiac function, but also ameliorated myocardial I/R-induced dysfunctional vasoconstriction and vasodilatation and degradation of endothelial structure in mesenteric arteries. VNS decreased serum and vascular levels of tumor necrosis factor-α and IL-1β. Interestingly, in vivo microdialysis studies demonstrated that VNS increased ACh concentration in the mesenteric circulation. Furthermore, VNS up-regulated expressions of muscarinic ACh receptors-3 (M
3
AChR) and α7nAChR in mesenteric arteries. Preserved endothelial relaxations by VNS were inhibited by atropine or methyllycaconitine, indicating that functional protection was associated with M
3
and α7nAChR activation. Finally, VNS increased STAT3 phosphorylation and inhibited NF-κB activation in mesenteric arteries, and these effects were abolished by α7nAChR shRNA treatment, indicating VNS-mediated anti-inflammatory effect mainly involved α7nAChR. These results demonstrated for the first time that VNS protected against remote vascular dysfunction, through the cholinergic anti-inflammatory pathway which is dependent on α7nAChR. Our findings represent a significant addition to the understanding of vagal nerve-mediated pathways and the potential roles they play in regulating the vasculature.
▶ Catalytic activity of Rh–NHC complexes in hydroformylation and hydrogenation was discussed. ▶ Theoretical and experimental results were related to the electronic properties of NHC ligands. ▶ ...Formation and reactivity of hydrido and hydrido carbonyl Rh–NHC complexes were presented.
Rhodium(I) complexes with N-heterocyclic carbenes (Rh–NHC) can be considered as important candidates for catalysts of hydroformylation of olefins. The high stability of Rh-C(NHC) bonding under reaction conditions allow to expect that NHC ligand will be present in coordination sphere of the catalytically active rhodium complex and therefore influences the reaction yield and regioselectivity. The potential applicability of Rh–NHC complexes containing chiral carbene ligand in asymmetric hydroformylation can be also considered. The excellent review articles relevant to application of Rh–NHC in hydroformylation have been published recently
1–3. After that, important contributions to this subject, concerning theoretical and experimental studies, both structural and catalytic, have been reported. Therefore, the reactivity of Rh–NHC complexes can be discussed now in term of these new data. The up to now reported results indicate that the most promising and selective systems for hydroformylation can be composed from Rh–NHC complex and stoichiometric amount of electron-withdrawing phosphorus ligand.
Postural instability is a common problem among older people, and it is associated with mobility impairments, activity limitation and fear of falling. The evaluation of postural control can contribute ...to the early detection of balance deficits and help health professionals to manage this problem to prevent falls in older adults. The aim of this study was to identify center of pressure cut-offs to differentiate between older adults with and without falls in the past 12 months. The participants were 170 older adults (mean age 67 years, 50 fallers and 120 non-fallers). Center of pressure area and sway velocity in the anterior-posterior and medio-lateral directions were assessed using a force platform during three 30s one-legged stance trials with eyes open. The mean across trials was used for analysis. The time-limit (how long the participant was able to stay in one-legged stance, up to 30s) was also assessed. Fallers had poorer postural control than non-fallers (effect size ≥ 0.52, P <0.05). The cut-offs identified were 10.3 cm2 for Center of pressure area, 2.9 cm/s for velocity in the anterior-posterior, and 3.4 cm/s for medio-lateral velocity. The force platform parameters obtained an area under the curve of 0.72, with sensitivity of 78% and specificity of 68%. There were no significant differences between non-fallers and fallers for time-limit variable (17 seconds vs. 18 seconds). Force platform parameters during one-legged stance were associated with history of falls in older adults. The cut-offs obtained acceptable area under curve, sensitivity and specificity, with center of pressure area presenting the best performance to differentiate between fallers and non-fallers.
An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA ND6 P25L mutation into the mouse. Mice with this mutation exhibited reduction in ...retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress.
This paper deals with the optimal reconfiguration problem of DC distribution networks by proposing a new mixed-integer nonlinear programming (MINLP) formulation. This MINLP model focuses on ...minimising the power losses in the distribution lines by reformulating the classical power balance equations through a branch-to-node incidence matrix. The general algebraic modelling system (GAMS) is chosen as a solution tool, showing in tutorial form the implementation of the proposed MINLP model in a 6-nodes test feeder with 10 candidate lines. The validation of the MINLP formulation is performed in two classical 10-nodes DC test feeders. These are typically used for power flow and optimal power flow analyses. Numerical results demonstrate that power losses are reduced by about 16% when the optimal reconfiguration plan is found. The numerical validations are made in the GAMS software licensed by Universidad Tecnológica de Bolívar.
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