scholarly journals Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Shu Li ◽  
Lina Wang ◽  
Xiuchuan Yan ◽  
Qinglan Wang ◽  
Yanyan Tao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Hepatic Fibrosis ◽  
Water Soluble ◽  
Salvianolic Acid B ◽  
Type I ◽  
Ang Ii ◽  
Radix Salviae Miltiorrhizae ◽  
Fibrotic Liver ◽  
Salvianolic Acid

The renin-angiotensin system (RAS) plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B), one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II) signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN-) induced rat fibrotic modelin vivoand Ang-II stimulated hepatic stellate cells (HSCs)in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R) and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I) andα-smooth muscle actin (α-SMA) productionin vitro, reduced the gene expression of transforming growth factor beta (TGF-β), and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation.

scholarly journals Proximal tubule NHE3 activity is inhibited by beta-arrestin-biased angiotensin II type 1 receptor signaling

2015 ◽  
Vol 309 (8) ◽  
pp. C541-C550 ◽  
Author(s):  
Carla P. Carneiro de Morais ◽  
Juliano Z. Polidoro ◽  
Donna L. Ralph ◽  
Thaissa D. Pessoa ◽  
Maria Oliveira-Souza ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
G Protein ◽  
Extracellular Fluid ◽  
The Body ◽  
Type I ◽  
Ang Ii ◽  
Receptor Signaling

Physiological concentrations of angiotensin II (ANG II) upregulate the activity of Na+/H+ exchanger isoform 3 (NHE3) in the renal proximal tubule through activation of the ANG II type I (AT1) receptor/G protein-coupled signaling. This effect is key for maintenance of extracellular fluid volume homeostasis and blood pressure. Recent findings have shown that selective activation of the beta-arrestin-biased AT1 receptor signaling pathway induces diuresis and natriuresis independent of G protein-mediated signaling. This study tested the hypothesis that activation of this AT1 receptor/beta-arrestin signaling inhibits NHE3 activity in proximal tubule. To this end, we determined the effects of the compound TRV120023, which binds to the AT1R, blocks G-protein coupling, and stimulates beta-arrestin signaling on NHE3 function in vivo and in vitro. NHE3 activity was measured in both native proximal tubules, by stationary microperfusion, and in opossum proximal tubule (OKP) cells, by Na+-dependent intracellular pH recovery. We found that 10−7 M TRV120023 remarkably inhibited proximal tubule NHE3 activity both in vivo and in vitro. Additionally, stimulation of NHE3 by ANG II was completely suppressed by TRV120023 both in vivo as well as in vitro. Inhibition of NHE3 activity by TRV120023 was associated with a decrease in NHE3 surface expression in OKP cells and with a redistribution from the body to the base of the microvilli in the rat proximal tubule. These findings indicate that biased signaling of the beta-arrestin pathway through the AT1 receptor inhibits NHE3 activity in the proximal tubule at least in part due to changes in NHE3 subcellular localization.

scholarly journals Novel Insights into the Antagonistic Effects of Losartan against Angiotensin II/AGTR1 Signaling in Glioblastoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4555
Author(s):  
Salvatore Panza ◽  
Rocco Malivindi ◽  
Amanda Caruso ◽  
Umberto Russo ◽  
Francesca Giordano ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
The Cancer Genome Atlas ◽  
Type I ◽  
Gene Promoters ◽  
Glioblastoma Cell ◽  
Ang Ii ◽  
Glioblastoma Cells ◽  
Estrogen Production

New avenues for glioblastoma therapy are required due to the limited mortality benefit of the current treatments. The renin-angiotensin system (RAS) exhibits local actions and works as a paracrine system in different tissues and tumors, including glioma. The glioblastoma cell lines U-87 MG and T98G overexpresses Angiotensin II (Ang II)/Angiotensin II type I receptor (AGTR1) signaling, which enhances in vitro and in vivo local estrogen production through a direct up-regulation of the aromatase gene promoters p I.f and p I.4. In addition, Ang II/AGTR1 signaling transactivates estrogen receptor-α in a ligand-independent manner through mitogen-activated protein kinase (MAPK) activation. The higher aromatase mRNA expression in patients with glioblastoma was associated with the worst survival prognostic, according to The Cancer Genome Atlas (TCGA). An intrinsic immunosuppressive glioblastoma tumor milieu has been previously documented. We demonstrate how Ang II treatment in glioblastoma cells increases programmed death-ligand 1 (PD-L1) expression reversed by combined exposure to Losartan (LOS) in vitro and in vivo. Our findings highlight how LOS, in addition, antagonizes the previously documented neoangiogenetic, profibrotic, and immunosuppressive effects of Ang II and drastically inhibits its stimulatory effects on local estrogen production, sustaining glioblastoma cell growth. Thus, Losartan may represent an adjuvant pharmacological tool to be repurposed prospectively for glioblastoma treatment.

scholarly journals Salvianolic Acid B-Alleviated Angiotensin II Induces Cardiac Fibrosis by Suppressing NF-κB Pathway In Vitro

2018 ◽  
Vol 24 ◽  
pp. 7654-7664 ◽  
Author(s):  
Chunhua Wang ◽  
Hong Luo ◽  
Yini Xu ◽  
Ling Tao ◽  
Churui Chang ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Fibrosis ◽  
Salvianolic Acid B ◽  
Salvianolic Acid

scholarly journals The Effect of Salvianolic Acid on Vascular Protection and Possible Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yalan Wu ◽  
Suowen Xu ◽  
Xiao Yu Tian
Keyword(s):  
Cardiovascular Diseases ◽  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Salvianolic Acid B ◽  
Drug Candidate ◽  
Protective Effects ◽  
Vascular Protection ◽  
Salvianolic Acid ◽  
Salvianolic Acid A

Salvia miltiorrhiza (Danshen), as an important traditional Chinese medicinal plant, has been used in China for the treatment of cardiovascular diseases for hundreds of years. Salvianolic acids (salvianolic acid A and salvianolic acid B) as the most abundant water-soluble component extracted from Salvia miltiorrhiza have attracted more and more attention from cardiovascular scientists due to its comprehensive cardiovascular actions. In vivo and in vitro studies have rendered salvianolic acid an excellent drug candidate for the treatment and prevention of cardiovascular diseases. In this review, we surveyed the protective effects of salvianolic acid A and salvianolic acid B against cardiovascular diseases and the pharmacological basis, providing a strong scientific rationale for elucidating the important role of Salvia miltiorrhiza in cardiovascular therapy. More importantly, we also hope to provide new inspiration and perspectives on the development and innovation of small-molecule cardiovascular drugs based on salvianolic acid.

scholarly journals Effects of Salvianolic Acid B on Protein Expression in Human Umbilical Vein Endothelial Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Tsong-Min Chang ◽  
Guey-Yueh Shi ◽  
Hua-Lin Wu ◽  
Chieh-Hsi Wu ◽  
Yan-Di Su ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Water Soluble ◽  
Salvianolic Acid B ◽  
Pharmacological Intervention ◽  
Dependent Manner ◽  
Radix Salviae Miltiorrhizae ◽  
Human Umbilical Vein ◽  
Salvianolic Acid ◽  
Umbilical Vein Endothelial Cells

Salvianolic acid B (Sal B), a pure water-soluble compound extracted from Radix Salviae miltiorrhizae, has been reported to possess potential cardioprotective efficacy. To identify proteins or pathways by which Sal B might exert its protective activities on the cardiovascular system, two-dimensional gel electrophoresis-based comparative proteomics was performed, and proteins altered in their expression level after Sal B treatment were identified by MALDI-TOF MS/MS. Human umbilical vein endothelial cells (HUVECs) were incubated at Sal B concentrations that can be reached in human plasma by pharmacological intervention. Results indicated that caldesmon, an actin-stabilizing protein, was downregulated in Sal B-exposed HUVECs. Proteins that showed increased expression levels upon Sal B treatment were vimentin, T-complex protein 1, protein disulfide isomerase, tropomyosin alpha, heat shock protein beta-1, UBX domain-containing protein 1, alpha enolase, and peroxiredoxin-2. Additionally, Sal B leads to increased phosphorylation of nucleophosmin in a dose-dependent manner and promotes proliferation of HUVECs. We found that Sal B exhibited a coordinated regulation of enzymes and proteins involved in cytoskeletal reorganization, oxidative stress, and cell growth. Our investigation would provide understanding to the endothelium protection information of Sal B.

A role for angiotensin II AT1 receptors in ureteric bud cell branching

2003 ◽  
Vol 285 (2) ◽  
pp. F199-F207 ◽  
Author(s):  
Igor V. Iosipiv ◽  
Mercedes Schroeder
Keyword(s):  
Angiotensin Ii ◽  
Type I Collagen ◽  
Branching Morphogenesis ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Type I ◽  
Ang Ii ◽  
Collagen Gels ◽  
Ureteric Bud

Gene-targeting studies in mice demonstrate that the renin-angiotensin system is required for the proper development of the renal medulla. In the absence of angiotensin II (ANG II) or the ANG II type 1 (AT1) receptor, mice exhibit poor papillary development and a severe urinary-concentrating defect. These findings imply that the ureteric bud (UB) and its branches are targets for ANG II actions during renal development. However, direct evidence linking ANG II with UB-branching morphogenesis does not exist. Using immunohistochemistry, we demonstrated that UB-derived epithelia express angiotensinogen (Ao) and the AT1 receptor during murine metanephrogenesis. Ao and AT1 receptors are expressed in the UB branches and to a lesser extent in the stromal mesenchyme. AT1 receptor expression in UB-derived epithelia increased from embryo day 12 to day 16 and was observed on both luminal and basolateral membranes. In accord with these findings, cultured murine UB cells express AT1 receptor protein and mRNA. Treatment of UB cells cultured in three-dimensional type I collagen gels with ANG II (10–7 to 10–5 M) elicits a dose-related increase in the number of cells that have primary and secondary branches. These effects of ANG II on UB branching are abrogated by pretreatment with the AT1 receptor antagonist candesartan. These data demonstrate a direct and independent role for ANG II acting via AT1 receptors on UB cell branching in vitro. The presence of Ao in the stroma and AT1 on UB cells supports the notion that cross talk between stroma and epithelial cells is crucial to epithelial branching morphogenesis in the developing kidney.

scholarly journals Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis

2012 ◽  
Vol 9 (1) ◽  
pp. 16 ◽  
Author(s):  
Hong-Ying Gao ◽  
Guo-Yu Li ◽  
Meng-Meng Lou ◽  
Xiao-Yu Li ◽  
Xiu-Yan Wei ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Fibrosis ◽  
Salvianolic Acid B ◽  
Hepatoprotective Effect ◽  
Salvianolic Acid

Interrenal activity in the female lizard Lagerta vivipara J.: In vitro response to ACTH 1–39 and to [SAR1, VAL5] angiotensin II (ANG II)

1988 ◽  
Vol 30 (1-6) ◽  
pp. 457-460 ◽  
Author(s):  
Chantal Dauphin-Villemant ◽  
François Leboulenger ◽  
Françoise Xavier ◽  
Hubert Vaudry
Keyword(s):  
Angiotensin Ii ◽  
Ang Ii ◽  
In Vitro Response ◽  
Female Lizard

Vasoconstriction of outer medullary vasa recta by angiotensin II is modulated by prostaglandin E2

1994 ◽  
Vol 266 (6) ◽  
pp. F850-F857 ◽  
Author(s):  
T. L. Pallone
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Regional Blood Flow ◽  
Renal Medulla ◽  
Hydraulic Pressure ◽  
Vascular Bundles ◽  
Ang Ii ◽  
Vasa Recta ◽  
Anatomical Arrangement

Vasa recta were dissected from outer medullary vascular bundles in the rat and perfused in vitro. Examination by transmission electron microscopy reveals them to be only outer medullary descending vasa recta (OM-DVR). To establish a method for systematic examination of vasoconstriction, OMDVR were perfused at 5 nl/min with collection pressure increased to 5 mmHg. Under these conditions, transmembrane volume flux was found to be near zero, and the transmural hydraulic pressure gradient was found to be < 15 mmHg. Over a concentration range of 10(-12) to 10(-8) M, abluminal application of angiotensin II (ANG II) caused graded focal vasoconstriction of OMDVR that is blocked by saralasin. Luminal application of ANG II over the same concentration range was much less effective. Abluminal application of prostaglandin E2 (PGE2) shifted the vasoconstrictor response of OMDVR to higher ANG II concentrations. PGE2 reversibly dilated OMDVR that had been preconstricted by ANG II. These results demonstrate that OMDVR are vasoactive segments. Their anatomical arrangement suggests that they play a key role in the regulation of total and regional blood flow to the renal medulla.

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