Document Detail


Angiotensin-(1-7) prevents diabetes-induced attenuation in PPAR-gamma and catalase activities.
MedLine Citation:
PMID:  20447391     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanisms by which angiotensin-(1-7) [Ang-(1-7)] exerts its beneficial effects on end-organ damage associated with diabetes and hypertension are not well understood. The purpose of this study was A) to compare the effects of apocynin with Ang-(1-7) on renal vascular dysfunction and NADPH oxidase activity in a combined model of diabetes and hypertension and B) to further determine whether chronic treatment with Ang-(1-7) can modulate renal catalase, and peroxisome proliferator activated receptor- gamma (PPAR-gamma) levels in streptozotocin-induced diabetes in both normotensive Wistar Kyoto rats (WKY) and in spontaneously hypertensive rats (SHR). Apocynin or Ang-(1-7) treatment for one month starting at the onset of diabetes similarly attenuated elevation of renal NADPH oxidase activity in the diabetic SHR kidney and reduced the degree of proteinuria and hyperglycemia, but had little or modest effect on reducing mean arterial pressure. Both drugs also attenuated the diabetes-induced increase in renal vascular responsiveness to endothelin-1. Induction of diabetes in WKY and SHR animals resulted in significantly reduced renal catalase activity and in PPAR-gamma mRNA and protein levels. Treatment with Ang-(1-7) significantly prevented diabetes-induced reduction in catalase activity and the reduction in PPAR-gamma mRNA and protein levels in both animal models. Taken together, these data suggest that activation of Ang-(1-7)-mediated signaling could be an effective way to prevent the elevation of NADPH oxidase activity and inhibition of PPAR-gamma and catalase activities in diabetes and/or hypertension.
Authors:
Gursev S Dhaunsi; Mariam H M Yousif; Saghir Akhtar; Mark C Chappell; Debra I Diz; Ibrahim F Benter
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-04
Journal Detail:
Title:  European journal of pharmacology     Volume:  638     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-04     Completed Date:  2010-09-27     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  108-14     Citation Subset:  IM    
Copyright Information:
(c) 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / administration & dosage,  pharmacology
Angiotensin I / administration & dosage,  pharmacology*
Animals
Antihypertensive Agents / administration & dosage,  pharmacology*
Antioxidants / administration & dosage,  pharmacology
Blood Glucose / drug effects
Blood Pressure / drug effects
Catalase / metabolism*
Diabetes Mellitus, Experimental / complications,  drug therapy,  metabolism*
Endothelin-1 / antagonists & inhibitors
Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / metabolism
Hyperglycemia / drug therapy
Hypertension / complications,  drug therapy,  metabolism,  physiopathology
Kidney / drug effects,  metabolism,  physiopathology
Male
NADPH Oxidase / metabolism
PPAR gamma / metabolism*
Peptide Fragments / administration & dosage,  pharmacology*
Proteinuria / drug therapy
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Renal Artery / drug effects
Grant Support
ID/Acronym/Agency:
HL-51952/HL/NHLBI NIH HHS; HL-56973/HL/NHLBI NIH HHS; P01 HL051952-150007/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Antihypertensive Agents; 0/Antioxidants; 0/Blood Glucose; 0/Endothelin-1; 0/PPAR gamma; 0/Peptide Fragments; 0/angiotensin I (1-7); 498-02-2/acetovanillone; 9041-90-1/Angiotensin I; EC 1.11.1.6/Catalase; EC 1.2.1.12/Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); EC 1.6.3.1/NADPH Oxidase
Comments/Corrections

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