The human duodenal mucosa harbors all components for a local renin angiotensin system

2019 ◽  
Vol 133 (8) ◽  
pp. 971-982 ◽  
Author(s):  
Emma Spak ◽  
Peter Hallersund ◽  
Anders Edebo ◽  
Anna Casselbrant ◽  
Lars Fändriks
Keyword(s):  
Renin Angiotensin System ◽  
Duodenal Mucosa ◽  
Gi Tract ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ussing Chambers ◽  
Duodenal Motility ◽  
Pharmacological Data ◽  
Per Oral

Abstract The renin-angiotensin system (RAS) is present in the gastrointestinal (GI) tract but remains to be fully characterized, particularly in man. The duodenum plays a role in both the upper and lower GI regulation, as well as in distant organs. The present study investigates the presence and functional potential of RAS in the human duodenal mucosa of healthy individuals. Endoscopically acquired mucosal biopsies from healthy volunteers were examined using western blot, immunohistochemistry, and ELISA. Functionality was examined by using Ussing chambers and recording duodenal transmucosal potential difference (PD) and motility in vivo. Angiotensinogen, Angiotensin II (AngII) and its receptors (AT1R, AT2R) as well as to the RAS associated enzymes renin, ACE, and neprylisin were detected in all samples of duodenal mucosa. Migrating motility complex induced elevations of transmucosal PD were significantly larger after per-oral administration of the AT1R receptor antagonist candesartan. Fasting duodenal motility per se was not influenced by candesartan. The epithelial current produced by duodenal mucosae mounted in Ussing chambers increased significantly after addition of AngII to specimens where the AT1R was blocked using losartan. The epithelial current also increased after addition of the AT2R-selective agonist C21. Immunostaining and pharmacological data demonstrate the presence of a local RAS in the human duodenal mucosa with capacity to influence epithelial ion transport by way of particulary the AT2R.

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.

Effects of Tokishakuyakusan, Keishibukuryogan, Shakuyakukanzoto and Unkeito on Ovarian Endothelin, Renin and Angiotensin II in Pregnant Mare's Serum Gonadotropin-treated Immature Rats

1992 ◽  
Vol 20 (02) ◽  
pp. 175-179 ◽  
Author(s):  
Satoshi Usuki ◽  
Yoshie Usuki ◽  
Junko Tanaka ◽  
Yuko Kawakura
Keyword(s):  
Angiotensin Ii ◽  
Herbal Medicines ◽  
Renin Angiotensin System ◽  
Concomitant Treatment ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Immature Rats ◽  
Serum Gonadotropin ◽  
Peptide System

We have previously proposed the ovarian ERAANPS (endothelin-renin-angiotensin-atrial natriuretic peptide system). The present study was undertaken to examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on endothelin-l (ET), renin and angiotensin II (A II) in the ovaries, of immature rats treated with 10 IU PMS for 48 h. ET and all components of renin-angiotensin system (RAS) were found at high levels in the ovary. Concomitant treatment with PMS plus TS, KB, SK or UT, especially TS and UT, tended to decrease the ET levels in ovary, while components of RAS tended to increase. However, ET, renin and A II levels in plasma were not at all affected after treatment with TS, KB, SK or UT. These results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS.

The Role of the Renin–Angiotensin System in the Cancer Stem Cell Niche

2021 ◽  
pp. 002215542110262
Author(s):  
Ethan J. Kilmister ◽  
Swee T. Tan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Renin Angiotensin System ◽  
Epidemiological Data ◽  
Malignant Cells ◽  
Angiotensin System ◽  
Renin Angiotensin

Cancer stem cells (CSCs) drive metastasis, treatment resistance, and tumor recurrence. CSCs reside within a niche, an anatomically distinct site within the tumor microenvironment (TME) that consists of malignant and non-malignant cells, including immune cells. The renin–angiotensin system (RAS), a critical regulator of stem cells and key developmental processes, plays a vital role in the TME. Non-malignant cells within the CSC niche and stem cell signaling pathways such as the Wnt, Hedgehog, and Notch pathways influence CSCs. Components of the RAS and cathepsins B and D that constitute bypass loops of the RAS are expressed on CSCs in many cancer types. There is extensive in vitro and in vivo evidence showing that RAS inhibition reduces tumor growth, cell proliferation, invasion, and metastasis. However, there is inconsistent epidemiological data on the effect of RAS inhibitors on cancer incidence and survival outcomes, attributed to different patient characteristics and methodologies used between studies. Further mechanistic studies are warranted to investigate the precise effects of the RAS on CSCs directly and/or the CSC niche. Targeting the RAS, its bypass loops, and convergent signaling pathways participating in the TME and other key stem cell pathways that regulate CSCs may be a novel approach to cancer treatment:

Temperature sensitivity of the renin-angiotensin system in Ambystoma tigrinum

1984 ◽  
Vol 246 (4) ◽  
pp. R510-R515 ◽  
Author(s):  
E. Corwin ◽  
G. M. Malvin ◽  
S. Katz ◽  
R. L. Malvin
Keyword(s):  
Temperature Sensitivity ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Competitive Inhibitor ◽  
Renin Activity ◽  
Ambystoma Tigrinum ◽  
Adrenergic System ◽  
Angiotensin System ◽  
Renin Angiotensin

The presence of a renin-angiotensin system was demonstrated in the poikilotherm Ambystoma tigrinum, commonly called the tiger salamander. Standard radioimmunoassay techniques were employed to measure the intrarenal renin activity (IRA) and the plasma renin activity (PRA) of A. tigrinum kept at either 5 or 20 degrees C. Basal IRA and PRA values were not affected by the temperature at which the animals were maintained. Intraperitoneal injection of the beta-adrenergic agonist isoproterenol, however, increased PRA only in those animals maintained at 20 degrees C. This is consistent with the hypothesis of a temperature sensitivity of the renal adrenergic system in vivo. In addition, we were able to demonstrate the existence of a contractile response of Ambystoma vascular smooth muscle to angiotensin II that was blocked by the competitive inhibitor saralasin.

scholarly journals Galectin-7 Impairs Placentation and Causes Preeclampsia Features in Mice

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1185-1194 ◽  
Author(s):  
Ellen Menkhorst ◽  
Wei Zhou ◽  
Leilani L. Santos ◽  
Sarah Delforce ◽  
Teresa So ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
First Trimester ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Elevated Systolic Blood Pressure ◽  
System Components ◽  
Pregnant Mice ◽  
New Treatment

Preeclampsia is a serious pregnancy-induced disorder unique to humans. The etiology of preeclampsia is poorly understood; however, poor placental formation is thought causal. Galectin-7 is produced by trophoblast and is elevated in first-trimester serum of women who subsequently develop preeclampsia. We hypothesized that elevated placental galectin-7 may be causative of preeclampsia. Here, we demonstrated increased galectin-7 production in chorionic villous samples from women who subsequently develop preterm preeclampsia compared with uncomplicated pregnancies. In vitro, galectin-7 impaired human first-trimester trophoblast outgrowth, increased placental production of the antiangiogenic sFlt-1 splice variant, sFlt-1-e15a , and reduced placental production and secretion of ADAM12 (a disintegrin and metalloproteinase12) and angiotensinogen. In vivo, galectin-7 administration (E8–E12) to pregnant mice caused elevated systolic blood pressure, albuminuria, impaired placentation (reduced labyrinth vascular branching, impaired decidual spiral artery remodeling, and a proinflammatory placental state demonstrated by elevated IL1β, IL6 and reduced IL10), and dysregulated expression of renin-angiotensin system components in the placenta, decidua, and kidney, including angiotensinogen, prorenin, and the angiotensin II type 1 receptor. Collectively, this study demonstrates that elevated galectin-7 during placental formation contributes to abnormal placentation and suggests that it leads to the development of preeclampsia via altering placental production of sFlt-1 and renin-angiotensin system components. Targeting galectin-7 may be a new treatment option for preeclampsia.

scholarly journals Vasculoprotective effects of rosiglitazone through modulating renin-angiotensin system in vivo and vitro

2011 ◽  
Vol 10 (1) ◽  
pp. 10 ◽  
Author(s):  
Liqun Ren ◽  
Naifeng Liu ◽  
Hong Zhi ◽  
Yingjuan Li ◽  
Yanzhi Li ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

Effects of angiotensin II, ACTH, and KCl on the adrenal renin-angiotensin system in the rat

1990 ◽  
Vol 122 (3) ◽  
pp. 369-373 ◽  
Author(s):  
Hiroyuki Sasamura ◽  
Hiromichi Suzuki ◽  
Ryuichi Kato ◽  
Takao Saruta
Keyword(s):  
Angiotensin Ii ◽  
Statistical Significance ◽  
Renin Angiotensin System ◽  
Plasma Aldosterone ◽  
Aldosterone Secretion ◽  
Plasma Aldosterone Concentration ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Captopril Treatment

Abstract Angiotensin II, ACTH and potassium chloride were administered to rats for 6 days and the effects on adrenal renin-like activity and adrenal angiotensin II/III immunoreactivity were investigated. Rats infused with angiotensin II(140 pmol/min) either ip or sc showed increases in adrenal angiotensin II/III immunoreactivity (p<0.05) and plasma aldosterone concentration (p<0.05), but no change in adrenal renin-like activity. Captopril treatment of angiotensin Il-infused rats caused a slight decrease in angiotensin II/III immunoreactivity which did not reach statistical significance. In contrast, rats treated with ACTH (Cortrosyn-Z, 3 IU/day, sc) showed an increase in adrenal renin-like activity (p<0.01), but no significant change in adrenal angiotensin II/III immunoreactivity. Rats treated with KCl in drinking water showed increases (p<0.05) in adrenal renin-like activity, adrenal angiotensin II/III immunoreactivity, and plasma aldosterone. These results suggest that angiotensin II, ACTH and potassium, three major regulators of aldosterone secretion by the adrenal gland, have different effects on the adrenal renin-angiotensin system when administered in vivo.

scholarly journals A Red Wine Vinegar Beverage can Inhibit the Renin-Angiotensin System: Experimental Evidence in Vivo

2005 ◽  
Vol 28 (7) ◽  
pp. 1208-1210 ◽  
Author(s):  
Sachiko Honsho ◽  
Atsushi Sugiyama ◽  
Akira Takahara ◽  
Yoshioki Satoh ◽  
Yuji Nakamura ◽  
...  
Keyword(s):  
Experimental Evidence ◽  
Red Wine ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Wine Vinegar
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