| 1. |
- Alterman, Mathias
(författare)
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Development of selective non-peptide angiotensin II type 2 receptor agonsists
- 2010
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Ingår i: jraas. Journal of the renin-angiotensin-aldosterone system. - : Hindawi Limited. - 1470-3203 .- 1752-8976. ; 11:1, s. 57-66
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Tidskriftsartikel (refereegranskat)abstract
- The development of the first drug-like selective angiotensin II type 2 (AT(2)) receptor agonist (22) derived from the non-selective angiotensin II type 1 (AT(1)) receptor/AT(2) receptor agonist L-162,313 is presented. Compound 22 with a K-i value of 0.4 nM for the AT(2) receptor and a K-i > 10 mu M for the AT(1) receptor induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhancesin vivo duodenal alkaline secretion in Sprague-Dawley rats and lowers the mean arterial blood pressure in anaesthetised spontaneously hypertensive rats. Thus, the peptidomimetic 22 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. In addition, Compound 22 has a bioavailability of 20-30% after oral administration and a half-life estimated to four hours in the rat. Compound 22 will therefore serve as a valuable research tool enabling studies of the function of the AT(2) receptor in more detail.
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| 2. |
- Björkman, Eleonora, 1981, et al.
(författare)
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Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy subjects and gastroesophageal reflux disease patients.
- 2015
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Ingår i: Journal of the renin-angiotensin-aldosterone system : JRAAS. - : Hindawi Limited. - 1752-8976 .- 1470-3203. ; 16:3, s. 570-577
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Tidskriftsartikel (refereegranskat)abstract
- The human esophageal mucosa expresses various components of the renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II (AngII). The aim of this study was to investigate the esophageal presence of angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV receptor (AT4R). The aim was also to study the actions of AngIV and to look for aberrations in patients with gastroesophageal reflux disease (GERD).
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| 3. |
- Bojestig, M, et al.
(författare)
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The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes
- 2000
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Ingår i: jraas. Journal of the renin-angiotensin-aldosterone system. - 1470-3203 .- 1752-8976. ; 1:4, s. 353-356
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Tidskriftsartikel (refereegranskat)abstract
- Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c. >8.4% compared with those with mean HbA1c 7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.
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| 4. |
- Casselbrant, Anna, 1970, et al.
(författare)
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The muscular expression of RAS in patients with achalasia.
- 2015
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Ingår i: Journal of the renin-angiotensin-aldosterone system : JRAAS. - : Hindawi Limited. - 1752-8976 .- 1470-3203. ; 16:3, s. 578-586
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II (AngII) elicits smooth muscle contractions via activation of AngII type 1 receptor (AT1R) in the intestinal wall and in sphincter regions in several species. Achalasia is a rare swallowing disorder and is characterized by a loss of the wave-like contraction that forces food through the oesophagus and a failure of the lower oesophageal sphincter to relax during swallowing.Aims and methods:The present study was undertaken to elucidate expression and distribution of a local renin-angiotensin system (RAS) in the muscular layer of distal normal human oesophagus as well as in patients with achalasia using western blot analysis, immunohistochemistry and polymerase chain reaction (PCR).
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| 5. |
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| 6. |
- Fiuza-Luces, C, et al.
(författare)
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Is the ACE I/D polymorphism associated with extreme longevity? A study on a Spanish cohort
- 2011
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Ingår i: Journal of the renin-angiotensin-aldosterone system : JRAAS. - : Hindawi Limited. - 1752-8976 .- 1470-3203. ; 12:3, s. 202-207
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Tidskriftsartikel (refereegranskat)abstract
- The 287 bp Ins(I)/Del(D) polymorphism [rs1799752] in intron 16 of the angiotensin-converting enzyme ( ACE) gene has been associated with extreme longevity (≥ 100 years) in some Caucasian and Asian cohorts, but this finding was not corroborated in other reports. We compared the allelic/genotypic frequency of the ACE I/D polymorphism among centenarians ( N = 64, 100—108 years, 89.1% female) and nonagenarians ( N = 47, 90—97 years, 76.6% female), and a control group of healthy young adults ( n = 434, age 20—40 years, 50% female). All participants were of the same Caucasian (Spanish) descent. The ACE I/D genotype met Hardy—Weinberg expectations in all the cohorts. Allelic and genotypic frequencies did not differ by sex in any of the study groups (all p > 0.2). There were no differences in allelic or genotypic frequencies between groups, for example the frequency of the D allele was 62.3% in controls vs. 65.3% in the elderly (64.8% in centenarians). In summary, the ACE I/D polymorphism is not significantly associated with extreme longevity in the Spanish population. Further research is, however, necessary using other approaches. It also remains to be determined if the interaction of ACE genotypes with some other genetic variants exerts a potential effect on longevity.
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| 7. |
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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. |
- Johansson, Maria E., et al.
(författare)
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Angiotensin type 2 receptor is expressed in human atherosclerotic lesions.
- 2008
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Ingår i: Journal of the renin-angiotensin-aldosterone system : JRAAS. - : Hindawi Limited. - 1470-3203 .- 1752-8976. ; 9:1, s. 17-21
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Expression of the angiotensin type 2 receptor (AT2-receptor) occurs in many animal models of atherosclerosis. However, its expression in human plaques and its functional role remains undetermined. This study examined AT2-receptor expression in human atherosclerotic plaque and also explored its potentially important functional role in atherosclerosis. MATERIAL AND METHODS: We analysed carotid atherosclerotic plaques obtained from 14 Caucasian patients who had previously undergone endarterectomy for symptomatic carotid artery stenosis. Half of all subjects received treatment with an angiotensin receptor blocker (ARB) (n=7); the remaining subjects received no intervention in the renin-angiotensin system (n=7). Immunohistochemistry measured tissue expression of smooth muscle cells (a-actin), macrophages (CD68 antibody), collagen (picro-sirius), and AT2-receptor (AT2-receptor antibody). RESULTS: AT2-receptor expression occurred consistently in all specimens. Although cellular localisation varied, AT2-receptor expression levels correlated with macrophage levels (p<0.01). Compared to conventional treatment, ongoing ARB treatment affected neither AT2-receptor levels nor plaque composition. CONCLUSIONS: AT2-receptor is expressed in human atherosclerotic plaque. Furthermore, we detected no functionally important role of AT2-receptor expression and found no evidence that ARB treatment regulates AT2-receptor expression.
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| 10. |
- Ljungberg, Liza, et al.
(författare)
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The association between circulating angiotensin-converting enzyme and cardiovascular risk in the elderly : A cross-sectional study.
- 2011
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Ingår i: jraas. Journal of the renin-angiotensin-aldosterone system. - London, United Kingdom : SAGE. - 1470-3203 .- 1752-8976. ; 12:3, s. 281-289
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: A polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with increased risk for cardiovascular disease (CVD). This polymorphism affects the level of circulating ACE, but there is great individual variation, even between those with the same genotype. Few previous studies have investigated the link between circulating ACE and cardiovascular risk. The aim of this study was to investigate this association, and to examine the relationship between ACE level, ACE genotype and CVD. MATERIALS AND METHODS: The study population consisted of 322 men and 350 women aged 69-87. Plasma ACE level was determined using enzyme-linked immunosorbent assay (ELISA), and ACE genotype was analysed using PCR followed by gel electrophoresis. RESULTS: In men, ACE levels increased with increasing number of cardiovascular risk factors (p = 0.003). There was a significant association in men between increased ACE level and both diabetes (p = 0.007) and smoking (p = 0.037). CONCLUSIONS: This study shows that cardiovascular risk factors (such as smoking and diabetes) are associated with higher levels of circulating ACE in men. High ACE levels may represent one of the cellular mechanisms involved in producing the vascular damage associated with cardiovascular risk factors.
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