title: Counteraction between angiotensin II and angiotensin-(1-7) via activating angiotensin type I and Mas receptor on rat renal mesangial cells.
abstract: In the updated concept of renin-angiotensin system (RAS), it contains the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-angtiogensin type 1 receptor (AT1) axis and the angiotensin-converting enzyme-related carboxypeptidase (ACE2)-Ang-(1-7)-Mas axis. The former axis has been well demonstrated performing the vasoconstrictive, proliferative and pro-inflammatory functions by activation of AT1 receptors, while the later new identified axis is considered counterbalancing the effects of the former. The present study is aimed at observing the interaction between Ang-(1-7) and Ang II on cultured rat renal mesangial cells (MCs). RT-PCR, Western blot and immunofluorescent staining and confocal microscopy results showed that both AT1 and Mas receptor were co-distributed in rat renal MCs. Ang-(1-7) showed similar effects on Ang II in cultured MCs that stimulated phosphorylated extracellular signal-regulated kinase (ERK)1/2 phosphorylation and transforms growth factor-β1 synthesis, and cell proliferation and extracellular matrix synthesis. Co-treatment of the cell with Ang-(1-7) and Ang II, Ang-(1-7) counteracted AngII-induced effects in a concentration dependent manner, but failed to alter the changes induced by endothelin-1. The stimulating effect of Ang II was mediated by AT1 receptor while all the effects of Ang-(1-7) were blocked by Mas receptor antagonist A-779, but not by AT1 receptor antagonist losartan or AT2 receptor antagonist PD123319. These results suggest that Ang-(1-7) and Ang II specifically interact with each other on rat renal MCs via activation of their specific receptors, Mas and AT1 receptor respectively.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ni
authors.forename: Tai
authors.initials: T
authors.lastname: Yao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.forename: Limin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019332:Endothelin-1 / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C092006:7-Ala-angiotensin (1-7); C524087:Agtrap protein, rat; D057911:Angiotensin Receptor Antagonists; D019332:Endothelin-1; D007093:Imidazoles; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D043562:Receptors, G-Protein-Coupled; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan