Endothelium-Derived Nitric Oxide Supports Renin Cell Recruitment Through the Nitric Oxide–Sensitive Guanylate Cyclase Pathway

Neubauer, Björn; Machura, Katharina; Kettl, Ramona; Lopez, Maria Luisa S. Sequeira; Friebe, Andreas; Kurtz, Armin

doi:10.1161/hypertensionaha.111.00221

Cited by 24 publications

(38 citation statements)

References 53 publications

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“…This upstream recruitment of renin-producing cells in renal vessels also occurs under stimulation of the RAAS by a drop of renal perfusion pressure for instance due to a renal artery stenosis or application of ACE inhibitors (Fig. 2) [71,75,85,104]. In response to severe salt-related challenges of the renin system such as salt loosing nephropathies, mutations or genetic deletions of the RAAS Fig.…”

Section: Introductionmentioning

confidence: 99%

Salt feedback on the renin-angiotensin-aldosterone system

Schweda

2014

Pflugers Arch - Eur J Physiol

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The renin-angiotensin-aldosterone system (RAAS) is a central element in the control of the salt and water balance of the body and arterial blood pressure. The activity of the RAAS is controlled by the protease renin, which is released from renal juxtaglomerular epithelioid cells (JGE cells) into the circulation. Renin release is regulated by a complex interplay of several locally acting hormones or mechanisms and longer feedback loops one of which involves salt intake. Acute NaCl loads or longer lasting high salt intakes suppress plasma renin activity, whereas reductions in NaCl intake stimulate it. Because the activation of the RAAS conserves the salt content of the body, a classical feedback loop between salt intake/body salt content and renin is established. Despite of its important role for body fluid homeostasis, the precise signaling pathways connecting salt intake with the synthesis and release of renin are only incompletely understood. Four putative controllers of the salt-dependent regulation of the RAAS have been suggested: (1) the macula densa mechanism which adjusts renin release in response to changes in the renal tubular salt concentration; (2) salt-dependent changes in the arterial blood pressure; (3) circulating salt-dependent hormones, particularly the atrial natriuretic peptide (ANP); and (4) renal sympathetic nervous activity, which is regulated by extracellular volume and arterial blood pressure. In this review, the role of these known controllers of the RAAS will be discussed with special emphasis on their relative contributions to the salt-dependent regulation of the RAAS at different time frames.

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Section: Introductionmentioning

confidence: 99%

Salt feedback on the renin-angiotensin-aldosterone system

Schweda

2014

Pflugers Arch - Eur J Physiol

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“…Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic renin phenotype (67), a process dependent on Notch (61) and endothelial nitric oxide (51).…”

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confidence: 99%

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Rider

Mullins

Verdon

et al. 2015

American Journal of Physiology-Renal Physiology

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Rider SA, Mullins LJ, Verdon RF, MacRae CA, Mullins JJ. Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium. Am J Physiol Renal Physiol 309: F531-F539, 2015. First published July 22, 2015 doi:10.1152/ajprenal.00247.2015.-Although renin is a critical regulatory enzyme of the cardiovascular system, its roles in organogenesis and the establishment of cardiovascular homeostasis remain unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but are highly restricted, specialized endocrine cells in adults. With a functional pronephros, embryonic zebrafish are ideal for delineating the developmental functions of renin-expressing cells and the mechanisms governing renin transcription. Larval zebrafish renin expression originates in the mural cells of the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal sites. The role of renin was determined by assessing responses to renin-angiotensin system blockade, salinity variation, and renal perfusion ablation. Renin expression did not respond to renal flow ablation but was modulated by inhibition of angiotensin-converting enzyme and altered salinity. Our data in larval fish are consistent with conservation of renin's physiological functions. Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show that Notch signaling and the endothelium are essential for developmental renin expression. After inhibition of angiogenesis, renin-expressing cells precede angiogenic sprouts. Arising from separate lineages, but relying on mutual interplay with endothelial cells, renin-expressing cells are among the earliest mural cells observed in larval fish, performing both endocrine and paracrine functions. renin; zebrafish; notch; endothelium; angiogenesis RENIN is the rate-limiting enzyme of the renin-angiotensin system (RAS). Mammalian ANG II, the effector of the RAS, is principally involved in blood pressure homeostasis by regulation of vasomotor tone and Na ϩ retention. ANG II also regulates cell proliferation and angiogenesis (12,22). Pathological activation of the RAS is associated with cardiovascular diseases, including hypertension and heart failure, and is consequently a major target of therapeutic agents (11).Renin and its cognate cells are required for normal renal development (2), including angiogenesis of the renal vascular tree (59). In mice, ablation of the renin gene or renin-expressing cells leads to renal developmental abnormalities (55,71,79). The vasculature of mammalian embryonic kidneys have a transient but extensive coverage of mural renin-expressing cells (17,31,32,47,63); however, their function is unclear. Adult renin-expressing cells are restricted to the juxtaglomerular apparatus and play a vital role in ion homeostasis by secreting activated renin enzyme via cytoplasmic granules (17,31,36,63). Upon physiological challenge by RAS inhibition or low Na ϩ , prearteriolar vascular smooth muscle cells (VSMC) reestablish their embryonic re...

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“…In addition, limited proliferation of renin-expressing cells can occur in this context. Retransformation of smooth muscle cells, but not of extraglomerular mesangial cells, appears to be dependent on the availability of nitric oxide, in particular, endothelium-derived nitric oxide (126).…”

Section: Plasticity Of Renin Productionmentioning

confidence: 95%

Plasticity of renal endocrine function

Kurt

Kurtz

2015

American Journal of Physiology-Regulatory, Integrative and Comp

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The kidneys are important endocrine organs. They secrete humoral factors, such as calcitriol, erythropoietin, klotho, and renin into the circulation, and therefore, they are essentially involved in the regulation of a variety of processes ranging from bone formation to erythropoiesis. The endocrine functions are established by cells, such as proximal or distal tubular cells, renocortical interstitial cells, or mural cells of afferent arterioles. These endocrine cells are either fixed in number, such as tubular cells, which individually and gradually upregulate or downregulate hormone production, or they belong to a pool of cells, which display a recruitment behavior, such as erythropoietin-and reninproducing cells. In the latter case, regulation of humoral function occurs via (de)recruitment of active endocrine cells. As a consequence renin-and erythropoietin-producing cells in the kidney show a high degree of plasticity by reversibly switching between distinct cell states. In this review, we will focus on the characteristics of renin-and of erythropoietin-producing cells, especially on their origin and localization, their reversible transformations, and the mediators, which are responsible for transformation. Finally, we will discuss a possible interconversion of renin and erythropoietin expression.calcitriol; erythropoietin; klotho; renin THE KIDNEYS FULFILL A VARIETY of functions, such as elimination of waste products of metabolism, regulation of fluid volume, and electrolyte concentrations and acid-base balance. Besides these excretory and homeostatic functions, the kidneys are endocrine organs essentially involved in the regulation of bone mineralization, blood pressure, and erythropoiesis. Thereto, the kidneys produce and secrete the hormones calcitriol, erythropoietin (EPO), klotho, and renin.Klotho, which exists in a membranous and a secreted form, regulates calcium and phosphate homeostasis (67, 83,129), thus contributing to bone mineralization. Membrane klotho functions mainly as a coreceptor for fibroblast growth factor (FGF) 23 (85, 178), which causes phosphaturia (85) and decreases circulating calcitriol levels (187) and renal phosphate resorption, resulting in reduced plasma phosphate levels. In its soluble form (66, 110), klotho mediates enhanced Ca 2ϩ (re)absorption in the kidney and in the intestine, by activating TRPV5 and TRPV6 (21, 23) channels. Missense mutations or deficiency of klotho result in hyperphosphatemia, hypercalcemia, and vascular calcification (64, 84,95,157).Calcitriol (34,35,138), the physiologically active form of vitamin D, contributes to bone mineralization by regulating homeostasis of calcium and phosphate through acting on the intestinal tract and the kidneys. Besides its role in regulation of calcium and phosphate homeostasis, calcitriol contributes to erythropoiesis (5, 48), as well as the activity of monocytes and macrophages (30). In contrast, proliferation and activity of T-lymphocytes and, thus, the adaptive immunity are suppressed by calcitriol (30). Vitamin D defi...

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Endothelium-Derived Nitric Oxide Supports Renin Cell Recruitment Through the Nitric Oxide–Sensitive Guanylate Cyclase Pathway

Cited by 24 publications

References 53 publications

Salt feedback on the renin-angiotensin-aldosterone system

Salt feedback on the renin-angiotensin-aldosterone system

Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium

Plasticity of renal endocrine function

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