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Renal pericytes: regulators of medullary blood flow
Get PDFRegulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla
Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?
Get PDFPericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important
The relationship between P2X4 and P2X7: a physiologically important interaction?
Get PDFPurinergic signaling within the kidney is becoming an important focus in the study of renal health and disease. The effectors of ATP signaling, the P2Y and P2X receptors, are expressed to varying extents in and along the nephron. There are many studies demonstrating the importance of the P2Y2 receptor on kidney function, and other P2 receptors are now emerging as participants in renal regulation. The P2X4 receptor has been linked to epithelial sodium transport in the nephron and expression levels of the P2X7 receptor are up-regulated in certain pathophysiological states. P2X7 antagonism has been shown to ameliorate rodent models of DOCA salt-induced hypertension and P2X4 null mice are hypertensive. Interestingly, polymorphisms in the genetic loci of P2X4 and P2X7 have been linked to blood pressure variation in human studies. In addition to the increasing evidence linking these two P2X receptors to renal function and health, a number of studies link the two receptors in terms of physical associations between their subunits, demonstrated both in vitro and in vivo. This review will analyze the current literature regarding interactions between P2X4 and P2X7 and assess the potential impact of these with respect to renal function
Inter-Cultural Limbo: The Dilemma of Western Education in Traditional Societies: Egypt as a Case-Study
Get PDFThe sense of belonging is a subjective perception. In traditional societies that are inherently conservative, cultural and religious the perception of the self becomes bound to the holistic context of the society. From the moment you are born you slowly submerge in a world where traditions, culture and the divinity of religion make up almost every aspect of one‟s daily life whether in public or in private. Slowly the society becomes a collective of individuals who work to safeguard traditions, culture and religious heritage. This holistic bond is, however, broken when a culture of individualism enshrined in the ideals of freedom and rights is instilled in the education and thus value system of those growing up in a traditional society. Meanwhile, the widening cultural gap between East and West renders the clash of civilizations more evident. Taking Egypt as a case-study, this paper examines the situation of those lying at the fault-line of this clash. What makes the situation of those lying at the fault-line of this clash more perplexing is the fact that Western education in Egypt has furthermore created an even wider cultural gap between those who receive such education and thus perceive themselves to be more „Western‟ and the rest of the society. To the West, Western educated Egyptians are, at the same time, never perceived as being part of this culture due to the fact that they are always put in the stereotypical category of „Arabs‟, „Middle Eastern‟ or „Muslims‟ thus hindering their integration in Western societies. They therefore usually find themselves in an inter-cultural limbo – neither belonging to their perceived nor to their normative culture. This paper intends to examine the correlation between education and identity and belongingness as applied in the case of Egypt
Campaigning for Change in Conflict Environments: A Case Study on Islamic Relief�s Development Programme Tackling Violence against Women in Iraq
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SAR mining and its application to the design of TRPA1 antagonists
Get PDFGiven the large amounts of screening data now available, empirical methods derived from matched- molecular pairs are being used as a means for suggesting bioisosteric replacements to the medicinal chemist. The pairwise analysis of compounds has been extended to the pairwise analysis of series to bring further context to these suggestions. A validation dataset derived from recent literature has been used to demonstrate that, given a series of active compounds, this approach would be expected to predict a more potent compound, if it exists, in around 46% of cases. The approach has been successfully applied to a series of TRPA1 antagonists
The Origins, Formation and Development of the Four Schools of Islamic Law
Get PDFAn examination of the early history and contemporary viewpoints on the four schools of Sunni Islamic jurisprudence
'"Strange to language": W.S. Graham and the Problematics of Verbal-Visual Communication'
Get PDFThis essay considers the relations between W.S. Graham's poetry and the paintings of his friend Bryan Wynter. It explores the ways in which Graham problematises the relations between word and image in his poem 'Wynter and the Grammarsow', and argues that what Graham and Wynter share above all is an investigation of the difficulties of representation. Both seek the means of forging a spontaneous connection with their subject or with their audience, and the pursuit of such directness leads them, paradoxically, down experimental paths, involving in their respective art forms the complex negotiation of different forms of movement
