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Local renin-angiotensin systems 总被引:6,自引:0,他引:6
A. H. Jan Danser 《Molecular and cellular biochemistry》1996,157(1-2):211-216
The existence of a local cardiovascular renin-angiotensin system (RAS) is often invoked to explain the long-term beneficial effects of RAS inhibitors in heart failure and hypertension. The implicit assumption is that all components of the RAS are synthesized in situ, so that local angiotensin II formation may occur independently of the circulating RAS. Evidence for this assumption however is lacking. The angiotensin release from isolated perfused rat hearts or hindlimbs depends on the presence of renal renin. When calculating the in vivo angiotensin production at tissue sites in humans and pigs, taking into account the extensive regional angiotensin clearance by infusing radiolabeled angiotensin I or II, it was found that angiotensin production correlated closely with plasma renin activity. Moreover, in pigs the cardiac tissue levels of renin and angiotensin were directly correlated with their respective plasma levels, and both in tissue and plasma the levels were undetectably low after nephrectomy. Similarly, rat vascular renin and angiotensin decrease to low or undetectable levels within 48 h after nephrectomy. Aortic renin has a longer half life than plasma renin, suggesting that renin may be bound by the vessel wall. In support of this assumption, both renin receptors and renin-binding proteins have been described. Like ACE, renin was enriched in a purified membrane fraction prepared from cardiac tissue. Binding of renin to cardiac or vascular membranes may therefore be part of a mechanism by which renin is taken up from plasma. It appears that the concept of a local RAS needs to be reassessed. Local angiotensin formation in heart and vessel wall does occur, but depends, at least under normal circumstances, on the uptake of renal renin from the circulation. Tissues may regulate their local angiotensin concentrations by varying the number of renin receptors and/or renin-binding proteins, the ACE level, the amount of metabolizing enzymes and the angiotensin receptor density.Abbreviations RAS
renin-angiotensin system
- ANG
angiotensin
- ACE
angiotensin-converting enzyme
- PRA
plasma renin activity 相似文献
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Martine de Boer Maaike te Lintel Hekkert Jiang Chang Bibi S. van Thiel Leonie Martens Maxime M. Bos Marion G. J. de Kleijnen Yanto Ridwan Yanti Octavia Elza D. van Deel Lau A. Blonden Renata M. C. Brandt Sander Barnhoorn Paula K. Bautista-Niño Ilona Krabbendam-Peters Rianne Wolswinkel Banafsheh Arshi Mohsen Ghanbari Christian Kupatt Leon J. de Windt A. H. Jan Danser Ingrid van der Pluijm Carol Ann Remme Monika Stoll Joris Pothof Anton J. M. Roks Maryam Kavousi Jeroen Essers Jolanda van der Velden Jan H. J. Hoeijmakers Dirk J. Duncker 《Aging cell》2023,22(3):e13768
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Abstract A class of very potent nucleoside transport inhibitors is present in two molecular forms around physiological pH. We investigated whether the monoprotonated or the unionized species of these molecules binds to this camer protein with higher affinity. 相似文献
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Christopher I Keeling Macaire MS Yuen Nancy Y Liao T Roderick Docking Simon K Chan Greg A Taylor Diana L Palmquist Shaun D Jackman Anh Nguyen Maria Li Hannah Henderson Jasmine K Janes Yongjun Zhao Pawan Pandoh Richard Moore Felix AH Sperling Dezene P W Huber Inanc Birol Steven JM Jones Joerg Bohlmann 《Genome biology》2013,14(3):R27
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A. Daneshjoo AH. Mokhtar N. Rahnama A. Yusof 《Biology of sport / Institute of Sport》2013,30(4):281-288
The study investigates the effects of the 11+ and HarmoKnee injury prevention programmes on knee strength in male soccer players. Under-21-year-old players (n=36) were divided equally into: the 11+, HarmoKnee and control groups. The programmes were performed for 24 sessions (20-25 min each). The hamstrings and quadriceps strength were measured bilaterally at 60°·s-1, 180°·s-1 and 300°·s-1. The concentric quadriceps peak torque (PT) of the 11+ increased by 27.7% at 300°·s-1 in the dominant leg (p<0.05). The concentric quadriceps PT of HarmoKnee increased by 36.6%, 36.2% and 28% in the dominant leg, and by 31.3%, 31.7% and 20.05% at 60°·s-1, 180°·s-1 and 300°·s-1 in the non-dominant leg respectively. In the 11+ group the concentric hamstring PT increased by 22%, 21.4% and 22.1% at 60°·s-1, 180°·s-1 and 300°·s-1, respectively in the dominant leg, and by 22.3%, and 15.7% at 60°·s-1 and 180°·s-1, in the non-dominant leg. In the HarmoKnee group the hamstrings in the dominant leg showed an increase in PT by 32.5%, 31.3% and 14.3% at 60°·s-1, 180°·s-1 and 300°·s-1, and in the non-dominant leg hamstrings PT increased by 21.1% and 19.3% at 60°·s-1 and 180°·s-1 respectively. The concentric hamstrings strength was significantly different between the 11+ and control groups in the dominant (p=0.01) and non-dominant legs (p=0.02). The HarmoKnee programme enhanced the concentric strength of quadriceps. The 11+ and HarmoKnee programmes are useful warm-up protocols for improving concentric hamstring strength in young professional male soccer players. The 11+ programme is more advantageous for its greater concentric hamstring strength improvement compared to the HarmoKnee programme. 相似文献
8.
Thomas Langerak Michelle Broekhuizen Peter-Paul Alexander Unger Lunbo Tan Marion Koopmans Eric van Gorp A. H. Jan Danser Barry Rockx 《PLoS neglected tropical diseases》2022,16(4)
A Zika virus (ZIKV) infection during pregnancy can result in severe birth defects such as microcephaly. To date, it is incompletely understood how ZIKV can cross the human placenta. Furthermore, results from studies in pregnant mice and non-human primates are conflicting regarding the role of cross-reactive dengue virus (DENV) antibodies on transplacental ZIKV transmission. Elucidating how ZIKV can cross the placenta and which risk factors contribute to this is important for risk assessment and for potential intervention strategies for transplacental ZIKV transmission. In this study we use an ex vivo human placental perfusion model to study transplacental ZIKV transmission and the effect that cross-reactive DENV antibodies have on this transmission. By using this model, we demonstrate that DENV antibodies significantly increase ZIKV uptake in perfused human placentas and that this increased uptake is neonatal Fc-receptor-dependent. Furthermore, we show that cross-reactive DENV antibodies enhance ZIKV infection in term human placental explants and in primary fetal macrophages but not in primary trophoblasts. Our data supports the hypothesis that presence of cross-reactive DENV antibodies could be an important risk factor for transplacental ZIKV transmission. Furthermore, we demonstrate that the ex vivo placental perfusion model is a relevant and animal friendly model to study transplacental pathogen transmission. 相似文献
9.
Ben M Minogue Stephen M Richardson Leo AH Zeef Anthony J Freemont Judith A Hoyland 《Arthritis research & therapy》2010,12(1):R22
Introduction
Nucleus pulposus (NP) cells have a phenotype similar to articular cartilage (AC) cells. However, the matrix of the NP is clearly different to that of AC suggesting that specific cell phenotypes exist. The aim of this study was to identify novel genes that could be used to distinguish bovine NP cells from AC and annulus fibrosus (AF) cells, and to further determine their expression in normal and degenerate human intervertebral disc (IVD) cells. 相似文献10.
Francine Z Marques Simon PR Romaine Matthew Denniff James Eales John Dormer Ingrid M Garrelds Lukasz Wojnar Katarzyna Musialik Barbara Duda-Raszewska Bartlomiej Kiszka Magdalena Duda Brian J Morris Nilesh J Samani AH Jan Danser Pawel Bogdanski Ewa Zukowska-Szczechowska Fadi J Charchar Maciej Tomaszewski 《Molecular medicine (Cambridge, Mass.)》2015,21(1):739-748
MicroRNA-181a binds to the 3′ untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) study. Renal immunohistochemistry and in situ hybridization showed that colocalization of miR-181a and renin was most prominent in collecting ducts where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA sequencing revealed that miR-181a was associated with downregulation of four mitochondrial pathways and upregulation of 41 signaling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure. 相似文献