title: Angiotensin type 2 receptor null mice express reduced levels of renal angiotensin II type 2 receptor/angiotensin (1-7)/Mas receptor and exhibit greater high-fat diet-induced kidney injury.
abstract: BACKGROUND
  Renin-angiotensin system (RAS) components exert diverse physiological functions and have been sub-grouped into deleterious angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin type 1 receptor (AT1R) and protective ACE2/angiotensin (1-7) (Ang-(1-7))/Mas receptor (MasR) axes. We have reported that chronic activation of angiotensin type 2 receptor (AT2R) alters RAS components and provides protection against obesity-related kidney injury.
  
  
  METHODS
  We utilized AT2R knockout (AT2KO) mice in this study and evaluated the renal expression of various RAS components and examined the renal injury after placing these mice on high fat diet (HFD) for 16 weeks.
  
  
  RESULTS
  The cortical ACE2 activity and MasR expression were significantly decreased in AT2KO mice compared to wild type (WT) mice. LC/MS analysis revealed an increase in renal Ang II levels and a decrease in Ang-(1-7) levels in AT2KO mice. Cortical expression of ACE and AT1R was increased but renin activity remained unchanged in AT2KO compared with WT mice. WT mice fed HFD exhibited increased systolic blood pressure, higher indices of kidney injury, mesangial matrix expansion score, and microalbuminuria, which were further increased in AT2KO mice.
  
  
  CONCLUSIONS
  This study suggests that deletion of AT2R decreases the expression of the beneficial ACE2/Ang-(1-7)/MasR and increases the deleterious ACE/Ang II/AT1R axis of the renal RAS in mice. Further, AT2KO mice are more susceptible to HFD-induced renal injury.
authors: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, USA.
authors: Quaisar
authors: Q
authors: Ali
authors: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, USA.
authors: Isha
authors: I
authors: Dhande
authors: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, USA.
authors: Preethi
authors: P
authors: Samuel
authors: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, USA thussain@central.uh.edu.
authors: Tahir
authors: T
authors: Hussain
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D002853:Chromatography, Liquid; D059305:Diet, High-Fat; D017353:Gene Deletion; D007668:Kidney / Q000293:injuries* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D013058:Mass Spectrometry; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System; D013599:Systole
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044139:Receptor, Angiotensin, Type 2; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin; C118790:angiotensin I (1-7)
keywords: Mas receptor; Renin–angiotensin system; angiotensin (1-7); angiotensin II type 2 receptor knockout