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- Casselbrant, Anna, 1970, et al.
(författare)
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Angiotensin II receptors are expressed and functional in human esophageal mucosa.
- 2009
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Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 297:5
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Tidskriftsartikel (refereegranskat)abstract
- Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT(1)) and type 2 (AT(2)) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT(1) and AT(2) receptors. Immunoreactivity to AT(1) and AT(2) was localized to stratum superficiale and spinosum in the epithelium. ACE, AT(1), and AT(2) were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT(1) receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was -6.4 mV, epithelial current (I(ep)) 34 muA/cm(2), and epithelial resistance (R(ep)) 321 Omega.cm(2). Serosal exposure to Ang II increased PD as a result of increased I(ep), whereas R(ep) was constant. Ang II given together with the selective AT(1)-receptor antagonist losartan, or AT(2) agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT(2)-receptor antagonist PD123319 did not influence PD, but I(ep) decreased and R(ep) increased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT(2)-receptor stimulation increases epithelial ion transport, whereas the AT(1) receptor inhibits ion transport and increases R(ep).
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- Docherty, Neil G., et al.
(författare)
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Urinary sodium excretion after gastric bypass surgery
- 2017
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289. ; 13:9, s. 1506-1514
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut-kidney signaling is implicated in sodium homeostasis and thus blood pressure regulation. Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity confers a pronounced and long-lasting blood pressure lowering effect in addition to significant weight loss. Objectives: We set out to establish whether RYGB is associated with an intrinsic change in urinary sodium excretion that may contribute to the reported blood pressure lowering effects of the procedure. Methods: Five female patients (age range: 28-50 yr) without metabolic or hypertensive co-morbidities were included in a study involving four 24-hour residential visits: once before surgery and 10 days, 3 months, and 20 months after surgery. Creatinine and sodium were measured in fasting plasma samples and 24-hour urine samples and creatinine clearance, estimated glomerular filtration rate, and indices of urinary sodium excretion were calculated. Fasting and 60-minute postprandial blood samples from each study day were assayed for pro-B-type natriuretic peptide (NT-proBNP). Results: Increases in weight-normalized urinary sodium excretion of up to 2.3-fold in magnitude occurred at 20 months after surgery. Median fractional excretion of sodium at 20 months was double that seen before surgery. Fasting NT-proBNP levels were stable or increased (1.5- to 5-fold). Moreover, a small postprandial increase in NT-proBNP was observed after surgery. Conclusions: Renal fractional excretion of sodium is increased after RYGB. A shift toward increased postoperative basal and meal associated levels of NT-proBNP coincides with increased urinary sodium excretion. The data support a working hypothesis that an enhanced natriuretic gut kidney signal after RYGB may be of mechanistic importance in the blood pressure lowering effects of this procedure. (C) 2017 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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- Elfvin, Anders, 1971, et al.
(författare)
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Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in Helicobacter pylori -infected humans
- 2014
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Ingår i: World Journal of Gastrointestinal Pathophysiology. - : Baishideng Publishing Group Inc.. - 2150-5330. ; 5:3, s. 373-379
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To compare a possible relation between Helico- bacter pylori (H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great im- portance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biop- sies using campylobacter-like organism test (CLO-test) and/or by using 14C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of induc- ible nitric oxide syntase (iNOS), nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase) my- eloperoxidase (MPO), and nitrotyrosine were assessed by Western blotting. RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age(mean)=39]andaH.pylori pos.group[n=8,m/ f = 5/3, age (mean) = 53]. Using western blot analy- sis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean ± SD being 12.6 ± 2.4vs 8.3 ± 3.1,P < 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of non- infected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean ± SD being 5.1 ± 3.4 vs 2.1 ± 1.9, P < 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47-phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a signifi- cantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the con- trols, mean ± SD being 3.1 ± 2.2vs 0.3 ± 0.2,P < 0.01. Regarding nitrotyrosine formation, Western blot did not show any significant increase or decrease compared to controls, 7.0 ± 0.9 vs 6.9 ± 1.1, not significant. CONCLUSION: iNOS, MPO and NADPH-oxidase was up-regulated among H. pylori infected. Regarding ni- trotyrosine no difference was found. This support an H. pylori related inhibition of radical formation.
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- Hallersund, Peter, 1975, et al.
(författare)
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Angiotensin II receptor expression and relation to Helicobacter pylori-infection in the stomach of the Mongolian gerbil.
- 2010
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Ingår i: BMC gastroenterology. - 1471-230X. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of the renin-angiotensin system in gastric physiology and disease has as yet been sparsely explored. The first aim of the study was to investigate the baseline presence and location of angiotensin II receptors (AT1R and AT2R) in the stomach of the Mongolian gerbil. A second aim was to elucidate whether the presence of H. pylori infection is associated with changes in the expression of these receptors. METHODS: H. pylori-negative and H. pylori-infected (strain SS1 or TN2GF4) male Mongolian gerbils were investigated. The stomachs were examined at six or 12 months after inoculation by the use of immunohistochemistry, western blot and microscopic morphometry. RESULTS: AT1R and AT2R were located in a variety of cells in the gerbil gastric wall, including a subpopulation of endocrine cells in the antral mucosa and inflammatory cells infiltrating H. pylori-infected stomachs. Gerbils infected with the SS1 strain showed a significantly increased antral AT1R protein expression and an increased number of infiltrating polymorphonuclear leucocytes (PMNs) at 12 months. The AT1R protein expression correlated with the number of PMNs and the antral expression of myeloperoxidase. CONCLUSIONS: Angiotensin II receptors are present in a variety of cells in the gastric wall of the Mongolian gerbil. The results indicate an influence dependent on the H. pylori strain on the gastric AT1R expression and a relationship between gastric AT1R expression and mucosal PMNs infiltration.
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| 7. |
- Hallersund, Peter, 1975
(författare)
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Impact of the upper gut on body fluid regulation and blood pressure in man - potential involvement of a locally expressed renin-angiotensin system
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explores the role of the upper gut in the regulation of diuresis and blood pressure control in relation to the novel finding of a mucosa-located renin-angiotensin system (RAS). RAS is a regulatory super-system vital for body fluid homeostasis and blood pressure control. Recent research demonstrates that RAS is not only an endocrine (blood borne) system, but also in all respects locally expressed influencing tissue growth and differentiation as well as inflammatory responses. A first aim of the present thesis-project was to explore if RAS was expressed in the mucosa of the stomach and duodenum. Indeed, by use of western blot and immunohistochemistry most components of RAS were found in several compartments of the gastric mucosa of the Mongolian gerbil (model for human Helicobacter pylori infection) and also in the human mucosa. It was also observed that a subset of gastric mucosal endocrine cells expressed AT1 receptors suggesting that activity in a local RAS can influence enteroendocrine signalling. RAS components were found also in the mucosa of the human duodenum. The second aim of the thesis was to examine the potential functionality of the local mucosal RAS described above. The project was focussed on a previously described sodium/volume sensor postulated to be situated in upper gut. Such a sensor is activated by food ingestion/drinking and increases renal diuresis already in the pre-absorptive state. The upper-gut location of this regulatory principle was demonstrated in healthy volunteers by intragastric instillation of 750 ml saline that almost promptly was followed by an increased diuresis, whereas intrajejunal instillation had an additional 60 min lag-time until response. In a second set of experiments, the volunteer were first exposed to gastric instillation of saline (with sham-intubation as time control) and after 30 to 40 min a gastroduodenoscopy with sampling of mucosal biopsies was performed. The tissue specimens were examined for RAS components and the principal finding was that the concentration of the pro-hormone angiotensinogen decreased in the duodenal mucosa, but not in the stomach. The results confirm that a volume sensor is located to the upper gut in man. Furthermore, local mucosal RAS, particularly in the duodenum, may be involved in mediating the diuresis occurring in the pre-absorptive state after drinking and eating. The third aim of the project was related to the physiological and clinical relevance of the sodium/volume monitor described above. Patients participating in the Swedish Obese Subjects (SOS) study were investigated. Gastric bypass (GBP), meaning that food and drinks are led directly into the jejunum thus bypassing the major part of the stomach and duodenum, was compared to gastric band constructions. The latter type of weight reducing surgery restricts the food intake capacity with the alimentary route intact. Interestingly, after adjustments for weight loss the GBP patients exhibited a larger 24h diuresis and a markedly more reduced systolic and diastolic pressure than the gastric band patients. These changes were prominent also 10 years after surgical intervention and were not related to the reduced body weight. Furthermore, the GBP patients consumed, despite a lowered blood pressure, approximately 1 g dietary salt more per day than patients operated with the restrictive banding techniques. This picture is compatible with that the sodium/volume sensor induces diuresis in an anticipatory fashion in relation to ingestive load and also inhibits salt appetite. Upon removal of this pre-absorptive regulatory mechanisms (as following GBP), more rough post-absorptive regulatory principles dominate that very probably results in an overshooting diuretic effect with depressor action and an increased salt intake.
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| 8. |
- Hallersund, Peter, 1975, et al.
(författare)
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The expression of renin-angiotensin system components in the human gastric mucosa.
- 2011
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Ingår i: Journal of the renin-angiotensin-aldosterone system : JRAAS. - : Hindawi Limited. - 1752-8976 .- 1470-3203. ; 12:1, s. 54-64
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: : The aim of the present study was to map the distribution of representative protein components of the renin-angiotensin system (RAS) in the human gastric mucosa. MATERIALS AND METHODS: : Biopsies from the antral and corporal mucosa of healthy Helicobacter pylori negative and positive volunteers were assessed by histology, Western blot and immunohistochemistry for angiotensin II subtype 1 and 2 receptors (AT1R, AT2R) and other RAS components (angiotensinogen, renin, angiotensin converting enzyme, and neprilysin). Mucosal levels of myeloperoxidase (MPO) served as a protein marker of neutrophil infiltration. RESULTS: : AT1R and AT2R were located in a variety of cells in the human gastric mucosa, including AT1R on a subpopulation of endocrine cells in the antral mucosa. Angiotensinogen and renin were expressed by resident mesenchymal cells in lamina propria. All investigated RAS components were found in vascular endothelial cells. The AT1R protein expression was 3-4 times higher in the gastric mucosa of H. pylori positive subjects compared to the gastric mucosa of H. pylori negative subjects (p<0.05). Gastric mucosal AT1R protein expression correlated positively with neutrophil infiltration (r=0.7, p<0.05). CONCLUSIONS: : Protein components of RAS are present in the human gastric mucosa. The results suggest an angiotensin II mediated impact on mucosal epithelial functions, antral endocrine properties, microvascular permeability, and gastric inflammation.
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| 9. |
- Spak, Emma, 1977, et al.
(författare)
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The human duodenal mucosa harbors all components for a local renin angiotensin system.
- 2019
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Ingår i: Clinical science (London, England : 1979). - 1470-8736. ; 133:8, s. 971-982
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Tidskriftsartikel (refereegranskat)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.
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