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William H Beierwaltes - One of the best experts on this subject based on the ideXlab platform.
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adenosine inhibits Renin Release from juxtaglomerular cells via an a1 receptor trpc mediated pathway
2013Co-Authors: Cecilia M Ortizcapisano, William H Beierwaltes, Pamela Harding, Douglas K Atchison, Robert D LasleyAbstract:Renin is synthesized and Released from juxtaglomerular (JG) cells. Adenosine inhibits Renin Release via an adenosine A1 receptor (A1R) calcium-mediated pathway. How this occurs is unknown. In cardi...
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calcium dependent phosphodiesterase 1c inhibits Renin Release from isolated juxtaglomerular cells
2009Co-Authors: Cecilia M Ortizcapisano, Pablo A Ortiz, Tang Dong Liao, William H BeierwaltesAbstract:Renin Release from the juxtaglomerular (JG) cell is stimulated by the second messenger cAMP and inhibited by calcium. We previously showed JG cells contain a calcium sensing receptor (CaSR), which,...
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adenylyl cyclase isoform v mediates Renin Release from juxtaglomerular cells
2007Co-Authors: Cecilia M Ortizcapisano, Jeffrey L. Garvin, Pablo A Ortiz, Pamela Harding, William H BeierwaltesAbstract:We have shown previously that decreasing intracellular calcium in the juxtaglomerular cells increases both cAMP formation and Renin Release. We hypothesized that this is because of an interaction between intracellular calcium and the calcium-inhibitable isoform of adenylyl cyclase, type-V. We used primary cultures of juxtaglomerular cells isolated from C-57/B6 mice at 70% to 80% confluence. Western blots were performed on isolated juxtaglomerular cells using antibodies against either of the 2 calcium inhibitable isoforms of adenylyl cyclase, types-V and -VI. Only the antibody against adenylyl cyclase-V gave us a strong band at 120 kDa as expected. Immunolabeling in juxtaglomerular cells with confocal microscopy found immunofluorescence for the adenylyl cyclase-V–specific antibody compared with either negative controls or cells stained with the adenylyl cyclase-VI antibody. Reducing isolated juxtaglomerular intracellular calcium with 100 μmol/L of the cytosolic calcium chelator BAPTA-AM stimulated both cAMP (3.49±0.70 to 10.09±0.81 pmol/mL per milligram of protein; P P
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decreased intracellular calcium stimulates Renin Release via calcium inhibitable adenylyl cyclase
2007Co-Authors: Cecilia M Ortizcapisano, Jeffrey L. Garvin, Pablo A Ortiz, Pamela Harding, William H BeierwaltesAbstract:Intracellular calcium and cAMP are the 2 second messengers that regulate Renin Release; cAMP stimulates Renin Release from juxtaglomerular (JG) cells, whereas increased intracellular calcium inhibits it. We hypothesized that decreased intracellular calcium acts by activating calcium-inhibitable isoforms of adenylyl cyclase, increasing cAMP, and stimulating Renin secretion. We used a primary culture of JG cells isolated from C-57/B6 mice. Cells were plated to a density of 70% in serum-free medium and incubated for 2 hours with or without 100 μmol/L of the cytosolic calcium chelator 5′5-dimethyl-1,2-bis-(2-aminophenoxy)-ethane-N,N,N′,N′-tetra-acetic acid (BAPTA-AM) to decrease intracellular calcium. JG cell cAMP content and Renin Release were determined by radioimmunoassay. Intracellular cAMP content was 4.04±0.92 pM/mL per milligram of protein, and it increased by125±33% ( P P
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endothelium derived relaxing factor regulates Renin Release in vivo
1992Co-Authors: David H Sigmon, Oscar A Carretero, William H BeierwaltesAbstract:Endothelium-derived relaxing factor (EDRF), through its inhibitory second messenger guanosine 3',5'-cyclic monophosphate (cGMP), inhibits Renin Release in vitro. To determine whether EDRF affects Renin in vivo, we tested whether EDRF synthesis inhibition could stimulate Renin secretion in intact rats. Because EDRF synthesis inhibition increases blood pressure and consequently withdraws sympathetic activity (both Renin inhibitory signals), we also studied the effect of L-N omega-nitroarginine methyl ester (L-NAME) when renal perfusion pressure was controlled and during beta-adrenergic blockade. Mean blood pressure (BP), heart rate (HR), and plasma Renin activity (PRA) were measured in anesthetized rats before and after EDRF synthesis inhibition by a 10 mg/kg body wt bolus of L-NAME. L-NAME decreased PRA by 67% [from 11.0 +/- 2.7 to 3.7 +/- 0.8 ng angiotensin I (ANG I).ml-1.h-1, n = 12; P less than 0.001], increased BP by 20 +/- 2 mmHg (P less than 0.001), and decreased HR from 332 +/- 8 to 312 +/- 9 beats/...
Roberto Levi - One of the best experts on this subject based on the ideXlab platform.
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the novel h2s donor 4 carboxy phenyl isothiocyanate inhibits mast cell degranulation and Renin Release by decreasing intracellular calcium
2016Co-Authors: Alice Marino, Valentina Citi, Alma Martelli, Vincenzo Calderone, Ming Fu, Rui Wang, Roberto LeviAbstract:Background and Purpose Hydrogen sulfide (H2S) modulates many pathophysiological processes, including inflammation and allergic reactions, in which mast cells act as major effector cells. IgE receptor (FceRI) cross-linking leads to an increase in intracellular calcium ([Ca+2]i), a critical step in mast cell degranulation. The aim of this study was to investigate the role of H2S in [Ca+2]i-dependent mast cell activation. Experimental Approach We investigated the effects of H2S, either endogenously produced or Released by the slow H2S donor 4-carboxy-phenyl isothiocyanate (PhNCS-COOH), on antigenic- and non-antigenic degranulation of native murine mast cells (BMMC), human (HMC-1) and rat (RBL-2H3) mast cell lines. We measured the Release of specific mast cell degranulation markers (β-hexosaminidase and Renin), as well as changes in [Ca+2]i and phosphorylation of proteins downstream of FceRI activation. Key Results Endogenously produced H2S inhibited antigen-induced degranulation in RBL-2H3. Similarly, H2S Released by PhNCS-COOH (10-300 μM) reduced, in a concentration-dependent manner, antigenic and non-antigenic degranulation and Renin Release in all mast cell types. Notably, PhNCS-COOH also prevented in a concentration-dependent mode the increase in [Ca+2]i elicited by Ca+2 ionophore, thapsigargin and FceRI activation. Moreover, PhNCS-COOH attenuated the phosphorylation of Syk, cPLA-2 and PLCγ1 in antigen-stimulated RBL-2H3 cells. Conclusion and Implications Collectively, our results demonstrate that, by attenuating the phosphorylation of proteins downstream of FceRI cross-linking on mast cells, H2S diminishes [Ca+2]i availability and thus, mast cell degranulation and Renin Release. These findings suggest that PhNCS-COOH could be a strategic therapeutic tool in mast cell-mediated allergic conditions. This article is protected by copyright. All rights reserved.
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e ntpdase1 cd39 modulates Renin Release from heart mast cells during ischemia reperfusion a novel cardioprotective role
2015Co-Authors: Silvia Aldi, Alice Marino, Kengo Tomita, Federico Corti, Ranjini Anand, Kim E Olson, Aaron J Marcus, Roberto LeviAbstract:Ischemia/reperfusion (I/R) elicits Renin Release from cardiac mast cells (MC), thus activating a local Renin-angiotensin system (RAS), culminating in ventricular fibrillation. We hypothesized that in I/R, neurogenic ATP could degranulate juxtaposed MC and that ecto-nucleoside triphosphate diphosphohydrolase 1/CD39 (CD39) on MC membrane could modulate ATP-induced Renin Release. We report that pharmacological inhibition of CD39 in a cultured human mastocytoma cell line (HMC-1) and murine bone marrow-derived MC with ARL67156 (100 µM) increased ATP-induced Renin Release (≥2-fold), whereas purinergic P2X7 receptors (P2X7R) blockade with A740003 (3 µM) prevented it. Likewise, CD39 RNA silencing in HMC-1 increased ATP-induced Renin Release (≥2-fold), whereas CD39 overexpression prevented it. Acetaldehyde, an I/R product (300 µM), elicited an 80% increase in ATP Release from HMC-1, in turn, causing an autocrine 20% increase in Renin Release. This effect was inhibited or potentiated when CD39 was overexpressed or silenced, respectively. Moreover, P2X7R silencing prevented ATP- and acetaldehyde-induced Renin Release. I/R-induced RAS activation in ex vivo murine hearts, characterized by Renin and norepinephrine overflow and ventricular fibrillation, was potentiated (∼2-fold) by CD39 inhibition, an effect prevented by P2X7R blockade. Our data indicate that by regulating ATP availability at the MC surface, CD39 modulates local Renin Release and thus, RAS activation, ultimately exerting a cardioprotective effect.
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histamine h4 receptors inhibit mast cell Renin Release in ischemia reperfusion via protein kinase ce dependent aldehyde dehydrogenase type 2 activation
2014Co-Authors: Silvia Aldi, Alice Marino, Kengo Tomita, Kenichi Takano, Kenichiro Koda, Noel Yanki Chan, Mariselis Salazarrodriguez, Robin L Thurmond, Roberto LeviAbstract:Renin Released by ischemia/reperfusion (I/R) from cardiac mast cells (MCs) activates a local Renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC Renin Release and consequent activation of this local RAS. We postulated that MC histamine H4-receptors (H4Rs), being Gαi/o-coupled, might activate a protein kinase C isotype–e (PKCe)–aldehyde dehydrogenase type-2 (ALDH2) cascade, ultimately eliminating MC-degranulating and Renin-releasing effects of aldehydes formed in I/R and associated arrhythmias. We tested this hypothesis in ex vivo hearts, human mastocytoma cells, and bone marrow–derived MCs from wild-type and H4R knockout mice. We found that activation of MC H4Rs mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of PKCe and ALDH2 in MCs, reducing aldehyde-induced MC degranulation and Renin Release and alleviating reperfusion arrhythmias. These cardioprotective effects are mimicked by selective H4R agonists and disappear when H4Rs are pharmacologically blocked or genetically deleted. Our results uncover a novel cardioprotective pathway in I/R, whereby activation of H4Rs on the MC membrane, possibly by MC-derived histamine, leads sequentially to PKCe and ALDH2 activation, reduction of toxic aldehyde-induced MC Renin Release, prevention of RAS activation, reduction of norepinephrine Release, and ultimately to alleviation of reperfusion arrhythmias. This newly discovered protective pathway suggests that MC H4Rs may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure.
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ige receptor mediated mast cell Renin Release
2014Co-Authors: Silvia Aldi, Kengo Tomita, Pablo A Robador, Annarita Di Lorenzo, Roberto LeviAbstract:Renin is a newly discovered constituent of mast cells. Given that mast cells play a major role in IgE-mediated allergic hypersensitivity, we investigated whether activation of the high-affinity IgE receptor FceRI elicits Release of mast-cell Renin. Cross-linking of FceRI on the surface of mature bone marrow–derived mast cells elicited Release of enzymatically active Renin protein. The angiotensin I–forming activity of the Renin protein was completely blocked by the selective Renin inhibitor BILA 2157, which excludes formation of angiotensin I by proteases other than Renin. FceRI-mediated mast-cell Renin Release was inhibited by dexamethasone and potentiated by the proinflammatory mediator PGE2. Furthermore, cross-linking of mast-cell FceRI in ex vivo murine hearts passively sensitized with monoclonal anti-DNP IgE also resulted in mast-cell degranulation and overflow of Renin. Our findings indicate that IgE-mediated allergic hypersensitivity provokes Release of Renin from both cultured and resident cardiac mast cells, a process likely to be exacerbated in a chronic inflammatory background. Given the widespread distribution of mast cells, and the presence of angiotensinogen and angiotensin-converting enzyme in many tissues, Renin Release in immediate hypersensitivity reactions could result in local angiotensin II generation and multiorgan dysfunctions.
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aldehyde dehydrogenase activation prevents reperfusion arrhythmias by inhibiting local Renin Release from cardiac mast cells
2010Co-Authors: Kenichiro Koda, Federico Corti, Noel Yanki Chan, Mariselis Salazarrodriguez, Racha Estephan, Randi B Silver, Daria Mochlyrosen, Roberto LeviAbstract:Background— Renin Released by ischemia/reperfusion from cardiac mast cells activates a local Renin-angiotensin system (RAS). This exacerbates norepinephrine Release and reperfusion arrhythmias (ventricular tachycardia and fibrillation), making RAS a new therapeutic target in myocardial ischemia. Methods and Results— We investigated whether ischemic preconditioning (IPC) prevents cardiac RAS activation in guinea pig hearts ex vivo. When ischemia/reperfusion (20 minutes of ischemia/30 minutes of reperfusion) was preceded by IPC (two 5-minute ischemia/reperfusion cycles), Renin and norepinephrine Release and ventricular tachycardia and fibrillation duration were markedly decreased, a cardioprotective anti-RAS effect. Activation and blockade of adenosine A2b/A3 receptors and activation and inhibition of protein kinase Ce (PKCe) mimicked and prevented, respectively, the anti-RAS effects of IPC. Moreover, activation of A2b/A3 receptors or activation of PKCe prevented degranulation and Renin Release elicited by ...
Armin Kurtz - One of the best experts on this subject based on the ideXlab platform.
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Renin Release sites mechanisms and control
2011Co-Authors: Armin KurtzAbstract:In the adult organism, systemically circulating Renin almost exclusively originates from the juxtaglomerular cells in the afferent arterioles of the kidneys. These cells share similarities with pericytes and myofibro-blasts. They store Renin in a vesicular network and granules and Release it in a regulated fashion. The Release mode of Renin is not understood; in particular, the involvement of SNARE proteins is unknown. Renin Release is acutely increased via the cAMP signaling pathway, which is triggered mainly by catecholamines and other G(s)-coupled agonists, and is inhibited by calcium-related pathways that are commonly activated by vasoconstrictors. Renin Release from juxtaglomerular cells is directly modulated in an inverse fashion by the blood pressure inside the afferent arterioles and by the chloride content in the tubule fluid at the macula densa segment of the distal tubule. Renin Release is stimulated by nitric oxide and by prostanoids Released by neighboring endothelial and macula densa cells. Steady-state Renin concentrations in the plasma are determined essentially by the number of Renin-producing cells in the afferent arterioles, which changes in parallel with challenges to the Renin-angiotensin-aldosterone system.
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regulation of Renin Release by local and systemic factors
2009Co-Authors: Frank Schweda, Armin KurtzAbstract:The Renin-angiotensin system (RAS) is critically involved in the regulation of the salt and volume status of the body and blood pressure. The activity of the RAS is controlled by the protease Renin, which is Released from the renal juxtaglomerular epithelioid cells into the circulation. Renin Release is regulated in negative feedbackloops by blood pressure, salt intake, and angiotensin II. Moreover, sympathetic nerves and renal autacoids such as prostaglandins and nitric oxide stimulate Renin secretion. Despite numerous studies there remained substantial gaps in the understanding of the control of Renin Release at the organ or cellular level. Some of these gaps have been closed in the last years by means of gene-targeted mice and advanced imaging and electrophysiological methods. In our review, we discuss these recent advances together with the relevant previous literature on the regulation of Renin Release.
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the calcium paradoxon of Renin Release calcium suppresses Renin exocytosis by inhibition of calcium dependent adenylate cyclases ac5 and ac6
2006Co-Authors: Christian Grunberger, Jurgen Klar, Armin Kurtz, Birgit Obermayer, Frank SchwedaAbstract:An increase in the free intracellular calcium concentration promotes exocytosis in most secretory cells. In contrast, Renin Release from juxtaglomerular (JG) cells is suppressed by calcium. The further downstream signaling cascades of this so called “calcium paradoxon” of Renin secretion have been incompletely defined. Because cAMP is the main intracellular stimulator of Renin Release, we hypothesized that calcium might exert its suppressive effects on Renin secretion via the inhibition of the calcium-regulated adenylate cyclases AC5 and AC6. In primary cultures of JG cells, calcium-dependent inhibitors of Renin Release (angiotensin II, endothelin-1, thapsigargin) suppressed Renin secretion, which was paralleled by decreases in intracellular cAMP levels [cAMP]. When [cAMP] was clamped by membrane permeable cAMP derivates, Renin Release was not suppressed by any of the calcium liberators. Additionally, both endothelin and thapsigargin suppressed cAMP levels and Renin Release in isoproterenol or forskolin-p...
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stimulation of Renin Release by prostaglandin e2 is mediated by ep2 and ep4 receptors in mouse kidneys
2004Co-Authors: Frank Schweda, Jurgen Klar, Shuh Narumiya, Rolf M Nusing, Armin KurtzAbstract:PGE2 is a potent stimulator of Renin Release. So far, the contribution of each of the four PGE2 receptor subtypes (EP1–EP4) in the regulation of Renin Release has not been characterized. Therefore,...
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cellular mechanism of Renin Release
2004Co-Authors: Frank Schweda, Armin KurtzAbstract:In this review we aim to give a comprehensive overview over the current knowledge of the cellular control of Renin Release. We hereby focus on the inhibitory effects of calcium on the exocytosis of Renin. After a short introduction into general aspects of the regulation of Renin Release, including a brief summary on the role of the second messengers cAMP and cGMP, we will discuss parts of the literature on the effects of calcium on the Renin system together with recent studies from our laboratory, investigating putative calcium influx and extrusion pathways of juxtaglomerular cells. Finally, as the precise mechanisms by which calcium inhibits the exocytosis of Renin are far from being understood, we will present some hypotheses on the intracellular events being involved in the suppression of Renin Release by calcium.
Cecilia M Ortizcapisano - One of the best experts on this subject based on the ideXlab platform.
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adenosine inhibits Renin Release from juxtaglomerular cells via an a1 receptor trpc mediated pathway
2013Co-Authors: Cecilia M Ortizcapisano, William H Beierwaltes, Pamela Harding, Douglas K Atchison, Robert D LasleyAbstract:Renin is synthesized and Released from juxtaglomerular (JG) cells. Adenosine inhibits Renin Release via an adenosine A1 receptor (A1R) calcium-mediated pathway. How this occurs is unknown. In cardi...
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calcium dependent phosphodiesterase 1c inhibits Renin Release from isolated juxtaglomerular cells
2009Co-Authors: Cecilia M Ortizcapisano, Pablo A Ortiz, Tang Dong Liao, William H BeierwaltesAbstract:Renin Release from the juxtaglomerular (JG) cell is stimulated by the second messenger cAMP and inhibited by calcium. We previously showed JG cells contain a calcium sensing receptor (CaSR), which,...
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adenylyl cyclase isoform v mediates Renin Release from juxtaglomerular cells
2007Co-Authors: Cecilia M Ortizcapisano, Jeffrey L. Garvin, Pablo A Ortiz, Pamela Harding, William H BeierwaltesAbstract:We have shown previously that decreasing intracellular calcium in the juxtaglomerular cells increases both cAMP formation and Renin Release. We hypothesized that this is because of an interaction between intracellular calcium and the calcium-inhibitable isoform of adenylyl cyclase, type-V. We used primary cultures of juxtaglomerular cells isolated from C-57/B6 mice at 70% to 80% confluence. Western blots were performed on isolated juxtaglomerular cells using antibodies against either of the 2 calcium inhibitable isoforms of adenylyl cyclase, types-V and -VI. Only the antibody against adenylyl cyclase-V gave us a strong band at 120 kDa as expected. Immunolabeling in juxtaglomerular cells with confocal microscopy found immunofluorescence for the adenylyl cyclase-V–specific antibody compared with either negative controls or cells stained with the adenylyl cyclase-VI antibody. Reducing isolated juxtaglomerular intracellular calcium with 100 μmol/L of the cytosolic calcium chelator BAPTA-AM stimulated both cAMP (3.49±0.70 to 10.09±0.81 pmol/mL per milligram of protein; P P
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decreased intracellular calcium stimulates Renin Release via calcium inhibitable adenylyl cyclase
2007Co-Authors: Cecilia M Ortizcapisano, Jeffrey L. Garvin, Pablo A Ortiz, Pamela Harding, William H BeierwaltesAbstract:Intracellular calcium and cAMP are the 2 second messengers that regulate Renin Release; cAMP stimulates Renin Release from juxtaglomerular (JG) cells, whereas increased intracellular calcium inhibits it. We hypothesized that decreased intracellular calcium acts by activating calcium-inhibitable isoforms of adenylyl cyclase, increasing cAMP, and stimulating Renin secretion. We used a primary culture of JG cells isolated from C-57/B6 mice. Cells were plated to a density of 70% in serum-free medium and incubated for 2 hours with or without 100 μmol/L of the cytosolic calcium chelator 5′5-dimethyl-1,2-bis-(2-aminophenoxy)-ethane-N,N,N′,N′-tetra-acetic acid (BAPTA-AM) to decrease intracellular calcium. JG cell cAMP content and Renin Release were determined by radioimmunoassay. Intracellular cAMP content was 4.04±0.92 pM/mL per milligram of protein, and it increased by125±33% ( P P
Raymond Ardaillou - One of the best experts on this subject based on the ideXlab platform.
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regulation of Renin Release is impaired after nitric oxide inhibition
1996Co-Authors: C Chatziantoniou, Jean Claude Dussaule, Marie Dominique Pauti, Florence Pinet, Dominique Promeneur, Raymond ArdaillouAbstract:Regulation of Renin Release is impaired after nitric oxide inhibition. The aim of the present study was dual: first to establish that a preparation of afferent arterioles freshly isolated from the rat kidney is a suitable model to study Renin Release and synthesis, and second to investigate the effect(s) of nitric oxide (NO) inhibition on Renin Release in this model. Purification of renal microvessels was based on iron oxide infusion into the kidneys and separation of the afferent arterioles from glomeruli and connective tissue with a magnet. These microvessels express preproRenin mRNA, contain Renin granules and Release Renin as evidenced by RT-PCR, immunocytochemistry and measurement of Renin activity, respectively. Renin secretion was increased in isolated afferent arterioles after in vivo treatment with the diuretic furosemide (+300%) or in vitro treatment with the adenylyl cyclase activator forskolin (+50%), indicating that this vascular preparation responds appropriately to regulators of the Renin-angiotensin system. Furthermore, in afferent arterioles isolated from control rats, Renin Release was positively correlated with total Renin content (r = 0.85). In afferent arterioles isolated from rats chronically treated with the NO-synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME), forskolin was ineffective in modifying Renin Release despite stimulation of cAMP levels. In addition, the correlation between Renin Release and tissue Renin content was disrupted. Similar results were obtained when cortical slices were used instead of afferent arterioles, suggesting that this defect in the regulation of Renin Release is independent of the presence of macula densa cells. To verify that the lack of regulation of Renin Release after L-NAME treatment was due to NO inhibition, the NO donor 3-morpholino-syndonimin-hydrochloride (SIN-1) was administered in afferent arterioles or cortical slices from kidneys of L-NAME-treated rats. In both preparations, SIN-1 reversed the L-NAME effect and re-established the responsiveness of Renin Release to forskolin and the relationship between Renin Release and Renin content. These data indicate that the adenylyl cyclase-mediated mechanism regulating Renin Release is impaired when NO synthesis is inhibited.
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angiotensin ii receptors and Renin Release in rat glomerular afferent arterioles
1994Co-Authors: C Chatziantoniou, Jean Claude Dussaule, William J Arendshorst, Raymond ArdaillouAbstract:Angiotensin II receptors and Renin Release in rat glomerular afferent arterioles. The purpose of recent studies was to investigate the expression of angiotensin II (Ang II) receptor sites in afferent arterioles freshly isolated from the rat kidney, and the role of Ang II on Renin Release by these vessels. The method of isolation and purification of renal microves-sels was based on iron oxide infusion into the kidneys and separation of the afferent arterioles from glomeruli and connective tissue with the aid of a magnetic field, successive passages through various sieves, and harvesting with collagenase. Ang II receptor characteristics were evaluated by radioligand binding studies using the non-peptide Ang II antagonists of AT 1 (Dup-753 and -532) and AT 2 (PD-123319 and CGP-42112) receptors. AT 1 antagonists displaced up to 80% of the Ang II binding with high affinity (3nM), whereas the remaining 20% showed low affinity for the Dup compounds and CGP-42112 (>10 µM), and intermediate affinity for PD-123319 (12 µM). These data suggest the existence of two Ang II receptor subtypes in the renal vasculature of the rat. In separate experiments, Renin Release by isolated afferent arterioles in vitro was 9 ng/hr/mg under control conditions. Ang II (0.1 µM) inhibited Renin secretion by 20%, whereas the adenylyl cyclase activator forskolin (10 µM) stimulated Renin secretion by 50%. In arterioles isolated from rats chronically treated with a converting enzyme inhibitor (perindoprilate) to reduce endogenous formation of Ang II, Renin Release increased 20-fold under control conditions in vitro and was further stimulated by forskolin. These results demonstrate that this preparation is a useful tool to study the functional role of Ang II and the control of Renin Release in the afferent arterioles.