Comparative study of three angiotensin II type 1 receptor antagonists in preventing liver fibrosis in diabetic rats: stereology, histopathology, and electron microscopy

2012 ◽  
Vol 43 (6) ◽  
pp. 723-735 ◽  
Author(s):  
Sare Sipal ◽  
Zekai Halici ◽  
İlhami Kiki ◽  
Beyzagul Polat ◽  
Abdulmecit Albayrak ◽  
...  
2009 ◽  
Vol 69 (1) ◽  
pp. 145-150 ◽  
Author(s):  
Masanori Iwase ◽  
Yuji Uchizono ◽  
Sakae Nohara ◽  
Nobuhiro Sasaki ◽  
Kazuo Sonoki ◽  
...  

2020 ◽  
Vol 318 (3) ◽  
pp. F683-F688 ◽  
Author(s):  
Malou Friederich-Persson ◽  
Patrik Persson

Exaggerated activation of the renin-angiotensin-aldosterone system (RAAS) is a key feature in diseases such as hypertension, diabetes, and chronic kidney disease. Recently, an intracellular RAAS was demonstrated with angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptors expressed in nuclei and mitochondria. Diabetes is associated with both mitochondrial dysfunction and increased intracellular ANG II concentration in the kidney cortex. The present study investigated the role of ANG II signaling in kidney cortex mitochondria isolated from control and streptozotocin-induced diabetic rats. Mitochondrial oxygen consumption was evaluated after addition of ANG II alone or after preincubation with candesartan (AT1 receptor antagonist), PD-123319 (AT2 receptor antagonist), or the two in combination. ANG II binds to only mitochondrial AT2 receptors in control rats and both AT1 receptors and AT2 receptors in diabetic rats. ANG II decreased oxygen consumption in mitochondria from both control and diabetic rats. ANG II response was reversed to increased oxygen consumption by the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. AT1 receptor inhibition did not affect the response to ANG II, whereas AT2 receptor inhibition abolished the response in mitochondria from control rats and reversed the response to increased oxygen consumption through superoxide-induced mitochondrial uncoupling in mitochondria from diabetic rats. ANG II decrease mitochondrial respiration via AT2 receptor-mediated nitric oxide release in both control and diabetic rats. AT1 receptors do not regulate mitochondria function in control rats, whereas ANG II via AT1 receptors increase mitochondria leak respiration in diabetic animals.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
ShaoBin LI ◽  
HeQin Zou ◽  
MinMin Gong ◽  
YuQin Chen ◽  
XiaoYong Yan ◽  
...  

Objective. This study aimed to investigate the effects of Ang-1 on neovascularization of diabetic organs by subcutaneous Matrigel angiogenesis model, established in type 1 diabetic rats. Methods. Ang-1 adenoviral vector was constructed. The rat model was established by STZ and divided into four group. The Matrigel was inserted subcutaneously into the abdominal cavity of rats at 8 weeks, the treatment group was injected with Ang-1 adenovirus vector via tail vein, and the rats were sacrificed at 10 weeks. Neovascularization of Matrigel was observed with transmission electron microscopy. The marker of vascular endothelial cell and pericyte were detected by immunofluorescence. Immunohistochemical detection of the neovascular endothelial junction protein was performed. RT-PCR was used to determine protein expression of neovascular in Matrigel. Results. Vascular cavity-like structure could be seen in subcutaneous Matrigel of diabetic rats, and the cavity was filled with a lot of red blood cells. Transmission electron microscopy showed that neovascular endothelial structure of the Matrigel was incomplete, while the Ang-1 treatment group had more vascular cavity-like structures, intact vascular endothelial structure, and reduced inflammatory cell infiltration in Matrigel. Additionally, the integrity of vascularization improved, and the marker of pericyte and the cell tight junctions protein was upregulated in Ang-1 treatment group. Conclusion. Hyperglycemia could induce pathological angiogenesis in subcutaneous Matrigel of diabetic rats, and Ang-1 could upregulate the expression of intercellular junction protein in subcutaneous Matrigel of diabetic rats and promote the integrity of neovascularization in the subcutaneous Matrigel of diabetic rats.


2009 ◽  
Vol 29 (3) ◽  
pp. 384-391 ◽  
Author(s):  
Sigrid Schulte ◽  
Annika Oidtmann ◽  
Norbert Kociok ◽  
Münevver Demir ◽  
Margarete Odenthal ◽  
...  

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