Chronic AT2 receptor activation increases renal ACE2 activity, attenuates AT1 receptor function and blood pressure in obese Zucker rats  Quaisar Ali,

Slides:



Advertisements
Similar presentations
Volume 66, Issue 6, Pages (December 2004)
Advertisements

Volume 65, Issue 6, Pages (June 2004)
Renin-stimulated TGF-β1 expression is regulated by a mitogen-activated protein kinase in mesangial cells  Y. Huang, N.A. Noble, J. Zhang, C. Xu, W.A.
Combination therapy with ACE inhibitors and angiotensin II receptor blockers in chronic renal disease: New therapeutic world beyond blood pressure reduction 
Cyril H. Barton, Zehnmin Ni, Nosratola D. Vaziri  Kidney International 
Volume 84, Issue 3, Pages (September 2013)
Volume 68, Issue 2, Pages (August 2005)
Volume 72, Issue 11, Pages (December 2007)
Volume 82, Issue 1, Pages 7-8 (July 2012)
Viper venom for diabetic nephropathy
Volume 88, Issue 4, Pages (October 2015)
Volume 72, Issue 11, Pages (December 2007)
Membranous nephropathy: When and how to treat
Viper venom for diabetic nephropathy
Prehypertension and chronic kidney disease: the ox or the plow?
Renin-stimulated TGF-β1 expression is regulated by a mitogen-activated protein kinase in mesangial cells  Y. Huang, N.A. Noble, J. Zhang, C. Xu, W.A.
John P. Middleton, Patrick H. Pun  Kidney International 
Volume 65, Issue 6, Pages (June 2004)
The renal sympathetic and renin-angiotensin response to lower body negative pressure in well-compensated cirrhosis  Florence Wong*, Kenneth Sniderman‡,
Epidermal growth factor receptor inhibition attenuates early kidney enlargement in experimental diabetes  Lesley Wassef, Darren J. Kelly, Richard E. Gilbert 
Vitamin E attenuates crystal formation in rat kidneys: Roles of renal tubular cell death and crystallization inhibitors  H.-S. Huang, J. Chen, C.-F. Chen,
Volume 87, Issue 1, Pages (January 2015)
The intrarenal renin-angiotensin system in hypertension
Volume 63, Issue 3, Pages (March 2003)
Nosratola D. Vaziri, Kaihui Liang, Yaoxian Ding  Kidney International 
Volume 54, Issue 4, Pages (October 1998)
Volume 56, Issue 5, Pages (November 1999)
Steven J. Rosansky, Richard J. Glassock  Kidney International 
Volume 67, Issue 3, Pages (March 2005)
Volume 66, Issue 2, Pages (August 2004)
Volume 61, Issue 6, Pages (June 2002)
Volume 75, Issue 2, Pages (January 2009)
Mitogen-activated protein kinase upregulation reduces renal D1 receptor affinity and G- protein coupling in obese rats  A.A. Banday, F.R. Fazili, A. Marwaha,
COX-2 inhibition attenuates endotoxin-induced downregulation of organic anion transporters in the rat renal cortex  Klaus Höcherl, Christoph Schmidt,
Volume 86, Issue 3, Pages (September 2014)
Volume 70, Issue 10, Pages (November 2006)
David M. Charytan, John P. Forman  Kidney International 
Special deLIVERy: podocyte injury promotes renal angiotensin II generation from liver- derived angiotensinogen  David I. Ortiz-Melo, Robert F. Spurney 
Volume 63, Issue 1, Pages (January 2003)
Volume 58, Issue 2, Pages (August 2000)
Reduced adenosine A2a receptor–mediated efferent arteriolar vasodilation contributes to diabetes-induced glomerular hyperfiltration  Patrik Persson, Peter.
Volume 82, Issue 3, Pages (August 2012)
Peroxisome proliferator-activated receptor-gamma agonist is protective in podocyte injury-associated sclerosis  H.-C. Yang, L.-J. Ma, J. Ma, A.B. Fogo 
Volume 66, Issue 6, Pages (December 2004)
The future of renoprotection: Frustration and promises
M.-J. Wu, M.-C. Wen, Y.-T. Chiu, Y.-Y. Chiou, K.-H. Shu, M.-J. Tang 
Methods for guideline development
Angiotensin II production and distribution in the kidney: I
Angiotensin II production and distribution in the kidney – II
Kaihui Liang, Nosratola D. Vaziri  Kidney International 
Volume 68, Issue 4, Pages (October 2005)
Circadian regulation of renal function
Volume 74, Issue 2, Pages (July 2008)
Volume 57, Issue 2, Pages (October 2000)
Volume 69, Issue 5, Pages (March 2006)
Dr Mahmood S. Mozaffari, Stephen W. Schaffer  Kidney International 
Volume 68, Issue 5, Pages (November 2005)
Volume 80, Issue 10, Pages (November 2011)
A functional immature model of chronic partial ureteral obstruction1
Salt sensitivity in genetically hypertensive rats of the Lyon strain
Volume 57, Issue 3, Pages (March 2000)
Does an apple a day put hypertension in play?
Volume 76, Issue 9, Pages (November 2009)
Volume 58, Issue 6, Pages (December 2000)
Volume 61, Issue 1, Pages (January 2002)
Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia  S. Faroqui, M. Levi,
Volume 53, Issue 5, Pages (May 1998)
Friends, social networks, and progressive chronic kidney disease
Volume 69, Issue 11, Pages (June 2006)
Volume 57, Issue 2, Pages (October 2000)
Presentation transcript:

Chronic AT2 receptor activation increases renal ACE2 activity, attenuates AT1 receptor function and blood pressure in obese Zucker rats  Quaisar Ali, Yonnie Wu, Tahir Hussain  Kidney International  Volume 84, Issue 5, Pages 931-939 (November 2013) DOI: 10.1038/ki.2013.193 Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 1 (a) Food, (b) water intake, (c) urinary volume, (d) urinary sodium excretion (UNaV), and (e) glomerular filtration rate (GFR) measured using fluorescein isothiocyanate–inulin clearance method in conscious control and CGP-treated lean and obese Zucker rats. *Significantly different compared with lean control rats, #significantly different compared with obese control rats. Values are represented as mean±s.e.m.; one-way analysis of variance followed by Neuman–Keuls test (P<0.05; N=5–7 in each group). LCT, lean control; LCGP, lean treated with CGP42112A; OCT, obese control; OCGP, obese treated with CGP42112A. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 2 Expression of (a) angiotensin type 1 receptor (AT1R) and (b) AT2R in the kidney cortex of control and CGP-treated lean and obese Zucker rats. Upper panels: representative western blots for respective proteins with loading control β-actin. Bar graphs: represent the ratios of densities of the respective protein bands and β-actin, i.e., AT1/β-actin, AT2/β-actin. *Significantly different compared with lean control rats. Values are represented as mean±s.e.m.; one-way analysis of variance followed by Neuman–Keuls test (P<0.05; N=5–7 in each group). LCT, lean control; LCGP, lean treated with CGP42112A; OCT, obese control; OCGP, obese treated with CGP42112A. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 3 Expression of (a) renin and (b) angiotensin-converting enzyme (ACE) in the kidney cortex of control and CGP-treated lean and obese Zucker rats. Upper panels: representative western blots for respective proteins with loading control β-actin. Bar graphs: represent the ratios of densities of respective protein bands and β-actin, i.e., renin/β-actin, ACE/β-actin. *Significantly different compared with lean control rats. Values are represented as mean±s.e.m.; one-way analysis of variance followed by Neuman–Keuls test (P<0.05; N=5–7 in each group). LCT, lean control; LCGP, lean treated with CGP42112A; OCT, obese control; OCGP, obese treated with CGP42112A. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 4 (a) ACE2 expression, (b) ACE2 activity, and (c) Mas receptor expression in the kidney cortex of control and CGP-treated lean and obese Zucker rats. Upper panels: representative western blots for respective proteins with loading control β-actin. For western blot only, bar graphs represent the ratios of densities of respective protein bands and β-actin, i.e., ACE2/β-actin, Mas receptor (MasR)/β-actin. $Significantly different compared with lean control rats, #significantly different compared with obese control rats. Values are represented as mean±s.e.m.; one-way analysis of variance followed by Neuman–Keuls test (P<0.05; N=5–7 in each group). *Significantly different compared with lean control. LCT, lean control; LCGP, lean treated with CGP42112A; OCT, obese control; OCGP, obese treated with CGP42112A. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 5 Liquid chromatography–mass spectrometry quantification of (a) Angiotensin II and (b) Angiotensin-(1–7) in the kidney cortex of control and CGP-treated lean and obese rats. #Significantly different compared with obese control rats, values are represented as mean±s.e.m.; one-way analysis of variance with Newman–Keuls test, P<0.05; N=5–7 in each group. LCT, lean control; LCGP, lean treated with CGP42112A; OCT, obese control; OCGP, obese treated with CGP42112A. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 6 Effect of candesartan (100μg/kg bolus) on (a) diuresis, (b) natriuresis, (c) mean arterial pressure, and (d) heart rate in control and CGP-treated obese Zucker rats. *Significantly different compared with control basal, #Significantly different compared with control candesartan. Values are represented as mean±s.e.m.; one-way analysis of variance followed by Neuman–Keuls test (P<0.05, N=5 rats in each group). OBCT, obese control; OCGP, obese treated with CGP42112A. UNaV, urinary Na volume. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 7 Effect of AT2R agonist and antagonist on (a) ACE2 activity, (b) Mas receptor (MasR) expression, (c) renin activity, and (d) angiotensin type 1 receptor (AT1R) expression. Upper panels: representative western blots for respective proteins with loading control β-actin. Bar graphs represent the ratios of densities of respective protein bands and β-actin, i.e, AT1/β-actin, Mas/β-actin. *Significantly different compared with control. Values are represented as mean±s.e.m.; one-way analysis of variance followed by Neuman–Keuls test (P<0.05, N=6–7 in each group). CT, control; CGP, CGP42112A; PD, PD123319; RFU, relative fluorescence unit. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 8 Schematic representation of the protocol used in the renal function study. Kidney International 2013 84, 931-939DOI: (10.1038/ki.2013.193) Copyright © 2013 International Society of Nephrology Terms and Conditions