The maintenance of cardiovascular homeostasis is highly dependent on tightly controlled interactions between the heart and the kidneys. Therefore, it is not surprising that a dysfunction in one organ ...affects the other. This interlinking relationship is aptly demonstrated in the cardiorenal syndrome. The characteristics of the cardiorenal syndrome state include alterations in neurohumoral drive, autonomic reflexes, and fluid balance. The evidence suggests that several factors contribute to these alterations. These may include peripheral and central nervous system abnormalities. However, accumulating evidence from animals with experimental models of congestive heart failure and renal dysfunction as well as humans with the cardiorenal syndrome suggests that alterations in neural pathways, from and to the kidneys and the heart, including the central nervous system are involved in regulating sympathetic outflow and may be critically important in the alterations in neurohumoral drive, autonomic reflexes, and fluid balance commonly observed in the cardiorenal syndrome. This review focuses on studies implicating neural pathways, particularly the afferent and efferent signals from the heart and the kidneys integrating at the level of the paraventricular nucleus in the hypothalamus to alter neurohumoral drive, autonomic pathways, and fluid balance. Further, it explores the potential mechanisms of action for the known beneficial use of various medications or potential novel therapeutic manipulations for the treatment of the cardiorenal syndrome. A comprehensive understanding of these mechanisms will enhance our ability to treat cardiorenal conditions and their cardiovascular complications more efficaciously and thoroughly.
Although communication between neurons is considered a function of the synapse, neurons also release neurotransmitter from their dendrites. We found that dendritic transmitter release coordinates ...activity across distinct neuronal populations to generate integrative homeostatic responses. We show that activity-dependent vasopressin release from hypothalamic neuroendocrine neurons in the paraventricular nucleus stimulates neighboring (∼100 μm soma-to-soma) presympathetic neurons, resulting in a sympathoexcitatory population response. This interpopulation crosstalk was engaged by an NMDA-mediated increase in dendritic Ca2+, influenced by vasopressin’s ability to diffuse in the extracellular space, and involved activation of CAN channels at the target neurons. Furthermore, we demonstrate that this interpopulation crosstalk plays a pivotal role in the generation of a systemic, polymodal neurohumoral response to a hyperosmotic challenge. Because dendritic release is emerging as a widespread process, our results suggest that a similar mechanism could mediate interpopulation crosstalk in other brain systems, particularly those involved in generating complex behaviors.
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•Proof of a signaling modality mediating interpopulation crosstalk in the brain•Dendritic VP release from neurosecretory neurons stimulates autonomic neurons•Crosstalk involves Ca2+-mediated activation of a CAN channel in autonomic neurons•This crosstalk is involved in the generation of polymodal homeostatic responses
Son et al. show dendritic vasopressin release from hypothalamic endocrine neurons, which activates distant preautonomic neurons and modulates homeostatic responses. The study characterizes the underlying signaling events and suggests that similar dendritic release may affect network regulation in other systems.
Angiotensin II (AngII) is a key neuropeptide that acting within the brain hypothalamic paraventricular nucleus regulates neurohumoral outflow to the circulation. Moreover, an exacerbated AngII action ...within the paraventricular nucleus contributes to neurohumoral activation in hypertension. Although AngII effects involve changes in paraventricular nucleus neuronal activity, the precise underlying mechanisms, cellular targets, and distribution of AngII receptors within the paraventricular nucleus remain largely unknown. Thus, whether AngII effects involve direct actions on paraventricular neurons, or whether it acts via intermediary cells, such as astrocytes, is still controversial. To address this important gap in our knowledge, we used a multidisciplinary approach combining patch-clamp electrophysiology in presympathetic paraventricular neurons and astrocytes, along with in vivo sympathetic nerve recordings and astrocyte-targeted gene manipulations. We present evidence for a novel mechanism underlying central AngII actions, which involves astrocytes as major intermediary cellular targets. We found that AngII type 1 receptor mRNA is expressed in paraventricular astrocytes. Moreover, we report that AngII inhibited glutamate transporter function, increasing in turn extracellular glutamate levels. This resulted in the activation of neuronal extrasynaptic NMDA (N-methyl-d-aspartate) receptors, increased presympathetic neuronal activity, enhanced sympathoexcitatory outflow, and increased blood pressure. Together, our studies support astrocytes as critical intermediary cell types mediating brain AngII regulation of the circulation and indicate that AngII-mediated neuronal and sympathoexcitatory effects are dependent on a unique neuroglial signaling modality involving nonsynaptic glutamate transmission.
This paper presents a detailed review of the fabrication of metal matrix composites through the stir-casting process and its processing issues. Metal matrix composites are prevalent materials among ...researchers and industries owing to their specific properties. These materials also offer the scope of tailoring the desired properties. There are several applications where metal matrix composites are superior to other conventional metal and alloys. However, it is evident that each type of manufacturing or fabrication process faces inherent problems and issues. The difference in properties of each constituent material such as density, melting point, strength, and severity of plastic deformation poses limitations to each processing method, either stir casting or powder metallurgy. This study attempts to reveal such processing issues of metal matrix composites by stir-casting processes.
Previously we have shown that increased expression of renal epithelial sodium channels (ENaC) may contribute to the renal sodium and water retention observed during chronic heart failure (CHF). The ...goal of this study was to examine whether renal denervation (RDN) changed the expressions of renal sodium transporters ENaC, sodium-hydrogen exchanger-3 proteins (NHE3), and water channel aquaporin 2 (AQP2) in rats with CHF. CHF was produced by left coronary artery ligation in rats. Four weeks after ligation surgery, surgical bilateral RDN was performed. The expression of ENaC, NHE3, and AQP2 in both renal cortex and medulla were measured. As a functional test for ENaC activation, diuretic and natriuretic responses to ENaC inhibitor benzamil were monitored in four groups of rats (Sham, Sham+RDN, CHF, CHF+RDN). Western blot analysis indicated that RDN (1 wk later) significantly reduced protein levels of α-ENaC, β-ENaC, γ-ENaC, and AQP2 in the renal cortex of CHF rats. RDN had no significant effects on the protein expression of kidney NHE3 in both Sham and CHF rats. Immunofluorescence studies of kidney sections confirmed the reduced signaling of ENaC and AQP2 in the CHF+RDN rats compared with the CHF rats. There were increases in diuretic and natriuretic responses to ENaC inhibitor benzamil in rats with CHF. RDN reduced the diuretic and natriuretic responses to benzamil in CHF rats. These findings suggest a critical role for renal nerves in the enhanced expression of ENaC and AQP2 and subsequent pathophysiology of renal sodium and water retention associated with CHF.
This is the first study to show in a comprehensive way that renal denervation initiated after a period of chronic heart failure reduces the expression of epithelial sodium channels and aquaporin 2 leading to reduced epithelial sodium channel function and sodium retention.
Purpose
This paper aims to develop an initial understanding of the Lean Six Sigma methodology since its inception and examine the few Lean Six Sigma dimensions as a research domain through a critical ...review of the literature.
Design/methodology/approach
The paper is structured in two-part. The first part of the paper attempts to dwell on the evolution of the Lean Philosophy and Six Sigma methodology individually and the emergence of Lean Six Sigma methodology, covered under the Lean Six Sigma: a historical outline section. The second part of the study examines the dimensions associated with Lean Six Sigma such as frameworks, critical success factors, critical failure factors, type of industry, performance metric, year, publisher and journal, based on a total of 223 articles published in 72 reputed journals from the year 2000 to 2019 as a literature review.
Findings
The adoption of Lean Six Sigma, as a continuous improvement methodology, has grown enormously in the manufacturing and few service sectors such as health care and higher education during the past decade. The study revealed that researchers came out with conceptual frameworks for the implementation of Lean Six Sigma, whereas the validation through case studies seems to be lacking. The integration of Lean Six Sigma and other approaches with a focus on sustainability and the environment has emerged as a research field. A few of the most common critical success and failure factors were identified from the articles studied during the study.
Research limitations/implications
This paper may not have included some of the studies due to the inaccessibility and selection criteria followed for the study.
Originality/value
This paper will provide an initial introduction on Lean, Six Sigma and Lean Six Sigma and research insights Lean Six Sigma to beginners such as students, researchers and entry-level professionals.
Abstract The sympathetic nervous system has been identified as a major contributor to the pathophysiology of chronic heart failure (CHF) and other diseases such as hypertension and diabetes, both in ...experimental animal models and patients. The kidneys have a dense afferent sensory innervation positioning it to be the origin of multimodal input to the central nervous system. Afferent renal nerve (ARN) signals are centrally integrated, and their activation results in a general increase in sympathetic tone, which is directed toward the kidneys as well as other peripheral organs innervated by the sympathetic nerves. In the central nervous system, stimulation of ARN increases the neuronal discharge frequency and neuronal activity in the paraventricular nucleus (PVN) of the hypothalamus. The activity of the neurons in the PVN is attenuated during iontophoretic application of glutamate receptor blocker, AP5. An enhanced afferent renal input to the PVN may be critically involved in dictating sympathoexcitation in CHF. Furthermore, renal denervation abrogates the enhanced neuronal activity within the PVN in rats with CHF, thereby possibly contributing to the reduction in sympathetic tone. Renal denervation also restores the decreased endogenous levels of neuronal nitric oxide synthase (nNOS) in the PVN of rats with CHF. Overall, these data demonstrate that sensory information originating in the kidney excites pre-autonomic sympathetic neurons within the PVN and this “renal-PVN afferent pathway” may contribute to elevated sympathetic nerve activity in hyper-sympathetic disease conditions such as CHF and hypertension.
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