scholarly journals Megalin, Proton Pump Inhibitors and the Renin–Angiotensin System in Healthy and Pre-Eclamptic Placentas

2021 ◽  
Vol 22 (14) ◽  
pp. 7407
Author(s):  
Yuan Sun ◽  
Lunbo Tan ◽  
Rugina I. Neuman ◽  
Michelle Broekhuizen ◽  
Sam Schoenmakers ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Proton Pump ◽  
Ex Vivo ◽  
Renin Angiotensin System ◽  
Placental Tissue ◽  
Brown Norway ◽  
Angiotensin Receptors ◽  
Placental Perfusion ◽  
Angiotensin System ◽  
Renin Angiotensin

Soluble Fms-like tyrosine kinase-1 (sFlt-1) is increased in pre-eclampsia. The proton pump inhibitor (PPI) lowers sFlt-1, while angiotensin increases it. To investigate whether PPIs lower sFlt-1 by suppressing placental renin–angiotensin system (RAS) activity, we studied gene expression and protein abundance of RAS components, including megalin, a novel endocytic receptor for prorenin and renin, in placental tissue obtained from healthy pregnant women and women with early-onset pre-eclampsia. Renin, ACE, ACE2, and the angiotensin receptors were expressed at identical levels in healthy and pre-eclamptic placentas, while both the (pro)renin receptor and megalin were increased in the latter. Placental prorenin levels were upregulated in pre-eclamptic pregnancies. Angiotensinogen protein, but not mRNA, was detectable in placental tissue, implying that it originates from maternal blood. Ex vivo placental perfusion revealed a complete washout of angiotensinogen, while prorenin release remained constant. The PPI esomeprazole dose-dependently reduced megalin/(pro)renin receptor-mediated renin uptake in Brown Norway yolk sac epithelial cells and decreased sFlt-1 secretion from placental villous explants. Megalin inhibition blocked angiotensinogen uptake in epithelial cells. In conclusion, our data suggest that placental RAS activity depends on angiotensinogen taken up from the maternal systemic circulation. PPIs might interfere with placental (pro)renin-AGT uptake/transport, thereby reducing angiotensin formation as well as angiotensin-induced sFlt-1 synthesis.

The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

2020 ◽  
Vol 27 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Izabela Guimarães Barbosa ◽  
Giulia Campos Ferreira ◽  
Diomildo Ferreira Andrade Júnior ◽  
Cássio Rocha Januário ◽  
André Rolim Belisário ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Cardiovascular Diseases ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Search Terms

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

Beta-adrenoceptor-mediated release of angiotensin II from mesenteric arteries

1986 ◽  
Vol 250 (1) ◽  
pp. H144-H148 ◽  
Author(s):  
M. Nakamaru ◽  
E. K. Jackson ◽  
T. Inagami
Keyword(s):  
Renin Angiotensin System ◽  
Ringer Solution ◽  
Mesenteric Arteries ◽  
Angiotensin Receptors ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Beta Adrenoceptor ◽  
Essential Components

Essential components of the renin-angiotensin system such as renin enzymes, angiotensinogen, converting enzyme, and angiotensin receptors have been found in vascular tissues. Locally generated angiotensin (ANG) II may regulate vascular tone by contracting vascular smooth muscle or potentiating sympathetic activity. Recently it was suggested that beta-adrenoceptor-induced enhancement of noradrenergic neurotransmission is mediated by the vascular renin-angiotensin system. The present study was designated to obtain direct evidence for the release of ANG II from the vasculature by beta-adrenoceptor activation. Isolated rat mesenteric arteries were perfused in vitro with Krebs-Ringer solution, and released ANG II was concentrated in a Sep-Pak C-18 cartridge connected to the perfusion system. High-pressure liquid chromatography combined with radioimmunoassay clearly demonstrated the presence of ANG I, II, and a small amount of ANG III in the perfusate. Isoproterenol (10(-9) - 10(-6) M) induced the enhancement of pressor responses to nerve stimulation. This effect was markedly suppressed by propranolol (5 X 10(-7) M), captopril (2 X 10(-6) M), or [Sar1-Ile8]ANG II (10(-6) M). Isoproterenol (10(-9) - 10(-6) M) caused increase in the release of ANG II from mesenteric arteries. The increase in ANG II release during isoproterenol (10(-6) M) infusion was blocked by propranolol (10(-6) M). Captopril (2 X 10(-6) M) also inhibited the increase in ANG II induced by isoproterenol. These results indicate that locally generated ANG II is released from isolated perfused rat mesenteric arteries and its release is mediated by beta-adrenoceptors.

scholarly journals Effects of Aging and Renin‐Angiotensin System (RAS) Blockade on the Intra‐renal RAS in Older Fischer 344 X Brown Norway Rats

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Sherry O Kasper ◽  
Shea Gilliam‐Davis ◽  
Leanne Groban ◽  
Christy S Carter ◽  
William E Sonntag ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Brown Norway ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fischer 344 ◽  
Effects Of Aging ◽  
Norway Rats

scholarly journals Synthesis and Secretion of Angiotensin II by the Prostate Gland in Vitro

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 392-398 ◽  
Author(s):  
Orla A. O’Mahony ◽  
Stewart Barker ◽  
John R. Puddefoot ◽  
Gavin P. Vinson
Keyword(s):  
Angiotensin Ii ◽  
Seminal Plasma ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Receptor Expression ◽  
Angiotensin Receptors ◽  
Lncap Cells ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Rat Prostate

The renin angiotensin system has been shown to have tissue-related functions that are distinct from its systemic roles. We showed that angiotensin II type 1 (AT1) receptors are present in mammalian sperm, and angiotensin II stimulates sperm motility and capacitation. In addition, angiotensin II is present in human seminal plasma at concentrations higher than found in blood. In testing the possibility that the prostate may be the source of seminal plasma angiotensin II, mRNA coding for angiotensinogen, (pro)renin, and angiotensin-converting enzyme were identified by RT-PCR in rat and human prostate and in prostate LNCaP cells, as well as the angiotensin receptors types 1 and 2 (AT1 and AT2) in human tissues and AT1 in rat. In human tissue, immunocytochemistry showed cellular colocalization of renin with the AT1 receptor in secretory epithelial cells. Confirmation of the capacity of the prostate to secrete angiotensin II was shown by the detection of immunoreactive angiotensin in media removed from rat prostate organ cultures and LNCaP cells. Rat prostate angiotensin secretion was enhanced by dihydrotestosterone, but LNCaP angiotensin was stimulated by estradiol. This stimulation was blocked by tamoxifen. Rat prostate AT1 receptor expression was much greater in prepuberal than in postpuberal rats but was not affected by a low-sodium diet. It was, however, significantly enhanced by captopril pretreatment. These findings all suggest the independence of prostate and systemic renin angiotensin system regulation. The data presented here suggest that the prostate may be a source of the secreted angiotensin II found in seminal plasma.

A novel angiotensin I isolated from an elasmobranch fish

1993 ◽  
Vol 139 (2) ◽  
pp. 281-285 ◽  
Author(s):  
Y. Takei ◽  
Y. Hasegawa ◽  
T. X. Watanabe ◽  
K. Nakajima ◽  
N. Hazon
Keyword(s):  
Tertiary Structure ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Bony Fishes ◽  
Elasmobranch Fish ◽  
Hormonal System ◽  
Vasopressor Activity

ABSTRACT It is believed that the renin-angiotensin system evolved initially in primitive bony fishes and is absent from elasmobranchs. We have isolated angiotensin I from the incubates of plasma and kidney extracts of an elasmobranch fish, Triakis scyllia, using eel vasopressor activity as an assay system. Its sequence was determined to be H-Asn-Arg-Pro-Tyr-Ile-His-ProPhe-Gln-Leu-OH. Dogfish angiotensin I is teleost-like because of an asparagine residue at position 1 but it is mammalian-like because of an isoleucine residue at position 5. The unique and most important substitution in dogfish angiotensin I is a proline residue at position 3 which may cause significant changes in its tertiary structure. A glutamine residue at position 9 is also unique among all angiotensin Is sequenced to date. Dogfish angiotensin I is more potent than rat angiotensin I in its vasopressor activity in the dogfish but the relationship is reversed in the rat. Thus angiotensin receptors as well as the hormone molecules appear to have evolved during vertebrate phylogeny. Our findings establish the elasmobranch renin-angiotensin system and support the hypothesis that the renin-angiotensin system is a phylogenetically old hormonal system which plays important roles in cardiovascular and fluid homeostasis. Journal of Endocrinology (1993) 139, 281–285

scholarly journals Role of the renin angiotensin system on bone marrow-derived stem cell function and its impact on skeletal muscle angiogenesis

2010 ◽  
Vol 42 (3) ◽  
pp. 437-444 ◽  
Author(s):  
Micheline M. de Resende ◽  
Timothy J. Stodola ◽  
Andrew S. Greene
Keyword(s):  
Skeletal Muscle ◽  
Bone Marrow ◽  
Endothelial Cell ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Renin Angiotensin System ◽  
Brown Norway ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

Autologous bone marrow cell (BMC) transplantation has been shown as a potential approach to treat various ischemic diseases. However, under many conditions BMC dysfunction has been reported, leading to poor cell engraftment and a failure of tissue revascularization. We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation (ES) is impaired in the SS/Mcwi rats and that this effect is related to a dysregulation of the renin angiotensin system (RAS) that is normalized by the replacement of chromosome 13 derived from the Brown Norway rat (SS-13BN/Mcwi consomic rats). The present study explored bone marrow-derived endothelial cell (BM-EC) function in the SS/Mcwi rat and its impact on skeletal muscle angiogenesis induced by ES. SS/Mcwi rats were randomized to receive BMC from: SS/Mcwi; SS-13BN/Mcwi; SS/Mcwi rats infused with saline or ANG II (3 ng·kg−1·min−1). BMC were injected in the stimulated tibialis anterior muscle of SS/Mcwi rats. Vessel density was evaluated in unstimulated and stimulated muscles after 7 days of ES. BMC isolated from SS/Mcwi or SS/Mcwi rats infused with saline failed to restore angiogenesis induced by ES. However, BMC isolated from SS-13BN/Mcwi and SS/Mcwi rats infused with ANG II effectively restored the angiogenesis response in the SS/Mcwi recipient. Furthermore, ANG II infusion increased the capacity of BM-EC to induce endothelial cell tube formation in vitro and slightly increased VEGF protein expression. This study suggests that dysregulation of the RAS in the SS/Mcwi rat contributes to impaired BM-EC function and could impact the angiogenic therapeutic potential of BMC.

scholarly journals Renin–Angiotensin–Aldosterone System Inhibitors in Patients with COVID-19: General Considerations and Clinical Implications

2020 ◽  
Vol 33 (1) ◽  
pp. 1-5
Author(s):  
Neiberg de Alcantara Lima ◽  
Pedro Yuri Paiva Lima ◽  
Ricardo Lessa de Castro Junior ◽  
Eric Martin Sieloff ◽  
Stela Maria Vitorino Sampaio
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Viral Transmission ◽  
Host Cells ◽  
Angiotensin Receptors ◽  
Clinical Implications ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin

Initially reported in China at the end of 2019, the coronavirus pandemic has now reached an international scale with more than 1.5 million cases worldwide and more than eighty thousands deaths by April 8th of this year. Recent studies have shown that the virus invades host cells by the angiotensin-converting enzyme 2 receptor, making it essential to viral transmission. Concerns have been raised about possible benefits and harms associated with the use of ACE inhibitors and angiotensin receptors blockers in these patients. However, there is lack of evidence to recommend even temporarily discontinuing renin-angiotensin system inhibitors/blockers in patients infected with the SARS-CoV-2.

Abstract 421: Cardiac Hypertrophy Induced by Swimming Exercise in Mice and the Cardiac Renin-Angiotensin System: The More, the Better?

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Santiago Alonso L Tobar ◽  
Douglas S Soares ◽  
Graziela H Pinto ◽  
Daniel S Caetano ◽  
Amanda Lopes ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Molecular Mechanisms ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Swimming Training ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Physiological Cardiac Hypertrophy ◽  
Wide Range

Cardiac hypertrophy is an adaptive process which is triggered by different mechanism in order to improve blood flow to organism and it may progress as physiological or pathological. Physical exercise offers a wide range hemodynamic stimulus; consequently it may modulate several molecular mechanisms associated to cardiac hypertrophy, for instance the local cardiac renin-angiotensin system (RAS). Thus, the aim of this study was to analyze the classical (ANGII/AT1) and alternative (ANG1-7/MAS) axis of the RAS in the cardiac muscle of mice submitted to exercise with different volumes/intensity training for the development of cardiac hypertrophy. Therefore, male Balb/c mice were divided in three groups: (i) Sedentary (SED), (ii) swimming training twice a day (T2), and (iii) swimming training three times a day with 2% of body weight overload (T3), for six weeks of training. The cardiac hypertrophy was assessed by the left ventricle weight and tibial length (LV/mm) ratio and cardiomyocytes cross-sectional area. Angiotensin peptides were analyzed by HPLC and angiotensin receptor measured by western blotting. We have also analyzed fibrosis by masson’s tricrome and the fetal genes reactivation was assessed by qRT-PCR. Both swimming training induced cardiac hypertrophy, the CHI for groups was T2 (6.34±0.44 mg/mm) and T3 (6.74 ± 0.70 mg/mm) compared to SED (5.55±0.5 mg/mm, p = 0.002). There was no observed change in the levels of angiotensin peptides ANG-I, ANG-II, and ANG1-7 between training groups and sedentary, however when we analyze angiotensin receptors, group T3 showed higher levels of AT1 when compared to SED (p=0.004), while MASR levels was higher in T2 compared to SED (0.017). Further, there was moderate reactivation of fetal genes as evidenced by increased in MHC-β expression observed in T3, but without fibrosis in either group. Our results suggest that increasing volumes/intensity of exercise beyond moderate does not influence the magnitude or the structural phenotype of physiological cardiac hypertrophy. However, it might promote the activation of molecular mechanisms involved in pathological cardiac hypertrophy.

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