The influence of extracellular and intracellular calcium on the secretion of renin

Atchison, Douglas K.; Beierwaltes, William H.

doi:10.1007/s00424-012-1107-x

Cited by 58 publications

(45 citation statements)

References 115 publications

(190 reference statements)

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“…In accordance with those studies, we found that the ultrastructure of those ectopic renin-expressing cells was similar to those of typical juxtaglomerular cells, which are characterized by numerous electron-dense renin storage vesicles (8). In juxtaglomerular cells, renin is released from these vesicles by compound exocytosis (27) triggered by the cAMP signaling pathway (5,14), which is further enhanced by lowering of the extracellular concentration of Ca 2ϩ (1,14,19). Renin secretion from AS Ϫ/Ϫ and WT kidneys was dose dependently stimulated by isoproterenol, which activates the cAMP pathway in juxtaglomerular cells by binding to ␤ 1 -adrenergic receptors (8).…”

Section: Discussionsupporting

confidence: 87%

“…It is physiologically mainly regulated via ␤ 1 -adrenergic and ANG II type 1 (AT 1 ) receptors and by the perfusion pressure in preglomerular arterioles (5,14), thus managing a controlled activity of the renin-angiotensin-aldosterone system (RAAS) in the sense of a negative feedback. Renin secretion from cells displays a peculiarity in the way that decreasing the availability of Ca 2ϩ enhances rather than impedes secretion (1,19). In addition, a yet unexplained function of the gap junction protein connexin (Cx)40 is essential for the proper control of renin secretion from juxtaglomerular cells (13,32).…”

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confidence: 99%

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Control of renin secretion from kidneys with renin cell hyperplasia

Kurt

Karger

Wagner

et al. 2014

American Journal of Physiology-Renal Physiology

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In states of loss-of-function mutations of the renin-angiotensin-aldosterone system, kidneys develop a strong hyperplasia of renin-producing cells. Those additional renin cells are located outside the classic juxtaglomerular areas, mainly in the walls of preglomerular vessels and most prominently in multilayers surrounding afferent arterioles. Since the functional behavior of those ectopic renin cells is yet unknown, we aimed to characterize the control of renin secretion from kidneys with renin cell hyperplasia. As a model, we used kidneys from mice lacking aldosterone synthase (AS⁻/⁻ mice), which displayed 10-fold elevations of renin mRNA and plasma renin concentrations. On the absolute level, renin secretion from isolated AS⁻/⁻ kidneys was more than 10-fold increased over wild-type kidneys. On the relative level, the stimulation of renin secretion by the β-adrenergic activator isoproterenol or by lowering of the concentration of extracellular Ca²⁺ was very similar between the two genotypes. In addition, the inhibitory effects of ANG II and of perfusion pressure were similar between the two genotypes. Deletion of connexin40 blunted the pressure dependency of renin secretion and the stimulatory effect of low extracellular Ca²⁺ on renin secretion in the same manner in kidneys of AS⁻/⁻ mice as in wild-type mice. Our findings suggest a high degree of functional similarity between renin cells originating during development and located at different positions in the adult kidney. They also suggest a high similarity in the expression of membrane proteins relevant for the control of renin secretion, such as β₁-adrenergic receptors, ANG II type 1 receptors, and connexin40.

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Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

Control of renin secretion from kidneys with renin cell hyperplasia

Kurt

Karger

Wagner

et al. 2014

American Journal of Physiology-Renal Physiology

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“…Furthermore, calcium has been identified as a regulator of the RAAS at the level of renin [18]. As shown in Figure 1C, calcium acutely inhibits juxtaglomerular cell release of renin via the calcium-sensing receptor (CaSR) [61*], whereas chronic hypercalcemia [62] and chronic stimulation of the CaSR [63] appear to increase plasma renin activity.…”

Section: Calcium- Pth- and Vitamin D-mediated Control Of The Raasmentioning

confidence: 99%

“…Arrows C-F show Ca-, PTH-, and Vitamin D-mediated control of the RAAS. (C) Ca acutely inhibits renin release, but chronic elevations in Ca may stimulate renin production [18]. (D) PTH augments the aldosterone response to AngII [19], and PTH receptors are expressed in aldosterone-producing cells [20].…”

Section: Figurementioning

confidence: 99%

Interactions between adrenal-regulatory and calcium-regulatory hormones in human health

Brown

Vaidya

2014

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of Review To summarize evidence characterizing the interactions between adrenal- and calcium-regulating hormones, and the relevance of these interactions to human cardiovascular and skeletal health. Recent Findings Human studies support the regulation of parathyroid hormone (PTH) by the renin-angiotensin-aldosterone system (RAAS): angiotensin II may stimulate PTH secretion via an acute and direct mechanism, whereas aldosterone may exert a chronic stimulation of PTH secretion. Studies in primary aldosteronism, congestive heart failure, and chronic kidney disease have identified associations between hyperaldosteronism, hyperparathyroidism, and bone loss, which appear to improve when inhibiting the RAAS. Conversely, elevated PTH and insufficient vitamin D status have been associated with adverse cardiovascular outcomes, which may be mediated by the RAAS. Studies of primary hyperparathyroidism implicate PTH-mediated stimulation of the RAAS, and recent evidence shows that the vitamin D-vitamin D receptor (VDR) complex may negatively regulate renin expression and RAAS activity. Ongoing human interventional studies are evaluating the influence of RAAS inhibition on PTH and the influence of VDR agonists on RAAS activity. Summary While previously considered independent endocrine systems, emerging evidence supports a complex web of interactions between adrenal and calcium-regulating hormones, with implications for human cardiovascular and skeletal health.

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“…It is not surprising, therefore, that a dependent relationship must exist between calcium homeostasis and the RAAS. Perhaps the most widely and detailed descriptions are the interactions of calcium and renin secretion by the juxtaglomerular and renal arteriolar cells(27-31). In contrast to almost all other interactions involving calcium-mediated signaling, in the case of renin release increasing calcium concentrations has an inhibitory effect.…”

Section: Introductionmentioning

confidence: 99%

The renin–angiotensin–aldosterone system and calcium-regulatory hormones

2015

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There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact in order to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies, and provide insight into the results of prior and on-going intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

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The influence of extracellular and intracellular calcium on the secretion of renin

Cited by 58 publications

References 115 publications

Control of renin secretion from kidneys with renin cell hyperplasia

Control of renin secretion from kidneys with renin cell hyperplasia

Interactions between adrenal-regulatory and calcium-regulatory hormones in human health

The renin–angiotensin–aldosterone system and calcium-regulatory hormones

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