Presentation Title

Modulation of Angiotensin II Binding and AT1 Receptor Expression in Experimental Alport Mouse Kidney

Speaker Credentials

DO

College

College of Pharmacy

Location

Nova Southeastern University, Davie, Florida, USA

Format

Poster

Start Date

16-2-2018 12:15 PM

End Date

16-2-2018 1:15 PM

Abstract

Objective: To measure AT1 angiotensin II (AngII) receptor (AT1R) expression in an animal model of Alport Syndrome (AS) to assess the association between these receptors and this disease. Background: AS is a progressive renal glomerular disease, causing kidney failure, and hearing and visual impairment, affecting up to 3% of children and 0.2% of adults with end-stage renal disease (ESRD). It is caused by mutation of a Type IV collagen gene. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) are the only treatments that slow progression towards ESRD in AS. Methods: Kidneys from 8-week-old Col4a3-/- (KO) and wild-type mice were assayed for AT1R using 125I-sarcosine1,isoleucine8AngII saturation binding assay and receptor autoradiography to determine receptor density, distribution and binding affinity. Results: There was a 48% decrease (pDvalues did not differ between the groups. Receptor autoradiography showed no difference in AT1R density between the groups (153 versus 149 fmoles/g wet weight). However, AT1R’s were more diffusely distributed in the KO kidneys. Conclusion: The density of AT1 receptors in the AS model kidney is reduced. This suggests that renoprotection with ACEi-ARB in AS is not linked to overexpression of renal AT1R. Funding: Peggy and Harold Katz Family Endowed Professorship (AF), Cardiovascular Neuroscience Fund.

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Feb 16th, 12:15 PM Feb 16th, 1:15 PM

Modulation of Angiotensin II Binding and AT1 Receptor Expression in Experimental Alport Mouse Kidney

Nova Southeastern University, Davie, Florida, USA

Objective: To measure AT1 angiotensin II (AngII) receptor (AT1R) expression in an animal model of Alport Syndrome (AS) to assess the association between these receptors and this disease. Background: AS is a progressive renal glomerular disease, causing kidney failure, and hearing and visual impairment, affecting up to 3% of children and 0.2% of adults with end-stage renal disease (ESRD). It is caused by mutation of a Type IV collagen gene. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) are the only treatments that slow progression towards ESRD in AS. Methods: Kidneys from 8-week-old Col4a3-/- (KO) and wild-type mice were assayed for AT1R using 125I-sarcosine1,isoleucine8AngII saturation binding assay and receptor autoradiography to determine receptor density, distribution and binding affinity. Results: There was a 48% decrease (pDvalues did not differ between the groups. Receptor autoradiography showed no difference in AT1R density between the groups (153 versus 149 fmoles/g wet weight). However, AT1R’s were more diffusely distributed in the KO kidneys. Conclusion: The density of AT1 receptors in the AS model kidney is reduced. This suggests that renoprotection with ACEi-ARB in AS is not linked to overexpression of renal AT1R. Funding: Peggy and Harold Katz Family Endowed Professorship (AF), Cardiovascular Neuroscience Fund.