title: Genetic deletion of the angiotensin-(1-7) receptor Mas leads to glomerular hyperfiltration and microalbuminuria.
abstract: Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascular and proliferative actions of angiotensin II. Here we evaluated effects of the angiotensin-(1-7) receptor Mas on renal physiology and morphology using Mas-knockout mice. Compared to the wild-type animals, Mas knockout mice had significant reductions in urine volume and fractional sodium excretion without any significant change in free-water clearance. A significantly higher inulin clearance and microalbuminuria concomitant with a reduced renal blood flow suggest that glomerular hyperfiltration occurs in the knockout mice. Histological analysis found reduced glomerular tuft diameter and increased expression of collagen IV and fibronectin in the both the mesangium and interstitium, along with increased collagen III in the interstitium. These fibrogenic changes and the renal dysfunction of the knockout mice were associated with an upregulation of angiotensin II AT1 receptor and transforming growth factor-beta mRNA. Our study suggests that Mas acts as a critical regulator of renal fibrogenesis by controlling effects transduced through angiotensin II AT1 receptors in the kidney.
authors.affiliation: Pediatric Nephrology Unit, Medicine Faculty, Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Sérgio V B
authors.initials: SVB
authors.lastname: Pinheiro
authors.affiliation: Department of Morphology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Anderson J
authors.initials: AJ
authors.lastname: Ferreira
authors.affiliation: Department of Morphology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Kitten
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Kátia D
authors.initials: KD
authors.lastname: da Silveira
authors.affiliation: Pediatric Nephrology Unit, Medicine Faculty, Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Deivid A
authors.initials: DA
authors.lastname: da Silva
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Sérgio H S
authors.initials: SHS
authors.lastname: Santos
authors.affiliation: Department of Morphology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Elisandra
authors.initials: E
authors.lastname: Gava
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Castro
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Júnio A
authors.initials: JA
authors.lastname: Magalhães
authors.affiliation: Department of Morphology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Renata K
authors.initials: RK
authors.lastname: da Mota
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Giancarla A
authors.initials: GA
authors.lastname: Botelho-Santos
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.affiliation: Department of Physiology and Biophysics, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Robson A S
authors.initials: RAS
authors.lastname: Santos
authors.affiliation: Pediatric Nephrology Unit, Medicine Faculty, Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil. Electronic address: acssilva@hotmail.com.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Simoes E Silva
mesh_terms: D000419:Albuminuria / Q000209:etiology* / Q000235:genetics; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D005353:Fibronectins / Q000096:biosynthesis; D005355:Fibrosis; D017353:Gene Deletion; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D005353:Fibronectins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D003094:Collagen