Document Detail

Angiotensin-(1-7) blockade attenuates captopril- or hydralazine-induced cardiovascular protection in spontaneously hypertensive rats treated with NG-nitro-L-arginine methyl ester.
MedLine Citation:
PMID:  21326110     Owner:  NLM     Status:  MEDLINE    
We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHRs) chronically treated with the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (SHR-l). NG-nitro-L-arginine methyl ester (80 mg/L) administration for 3 weeks increased mean arterial pressure (MAP) from 196 ± 6 to 229 ± 3 mm Hg (P < 0.05). Treatment of SHR-l with Ang-(1-7) antagonist [d-Ala7]-Ang-(1-7) (A779; 744 μg·kg(-1)·d(-1) ip) further elevated MAP to 253 ± 6 mm Hg (P < 0.05 vs SHR-l or SHR). Moreover, A779 treatment attenuated the reduction in MAP and proteinuria by either captopril (300 mg/L in drinking water) or hydralazine (1.5 mg·kg(-1)·d(-1) ip). In isolated perfused hearts, the recovery of left ventricular function from global ischemia was enhanced by captopril or hydralazine treatment and was exacerbated with A779. The Ang-(1-7) antagonist attenuated the beneficial effects of captopril and hydralazine on cardiac function. Recovery from global ischemia was also improved in isolated SHR-l hearts acutely perfused with captopril during both the perfusion and reperfusion periods. The acute administration of A779 reduced the beneficial actions of captopril to improve recovery after ischemia. We conclude that during periods of reduced nitric oxide availability, endogenous Ang-(1-7) plays a protective role in effectively buffering the increase in blood pressure and renal injury and the recovery from cardiac ischemia. Moreover, Ang-(1-7) contributes to the blood pressure lowering and tissue protective actions of captopril and hydralazine in a model of severe hypertension and end-organ damage.
Ibrahim F Benter; Mariam H M Yousif; Fatemah M Al-Saleh; Raj Raghupathy; Mark C Chappell; Debra I Diz
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  57     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-16     Completed Date:  2011-09-16     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  559-67     Citation Subset:  IM    
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
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MeSH Terms
Angiotensin I / antagonists & inhibitors*,  pharmacology
Angiotensin II / administration & dosage,  analogs & derivatives,  pharmacology
Antihypertensive Agents / administration & dosage,  pharmacology,  therapeutic use*
Blood Glucose / analysis
Blood Pressure / drug effects
Brain / drug effects,  metabolism
Captopril / administration & dosage,  pharmacology,  therapeutic use*
Cytokines / immunology
Heart / drug effects*
Hydralazine / administration & dosage,  pharmacology,  therapeutic use*
Hypertension / drug therapy*,  metabolism,  physiopathology
Insulin / blood
Kidney / drug effects,  immunology,  metabolism
Leptin / blood
Myocardial Contraction / drug effects
Myocardial Reperfusion Injury / physiopathology,  prevention & control
NG-Nitroarginine Methyl Ester / pharmacology
Peptide Fragments / administration & dosage,  antagonists & inhibitors*,  pharmacology
Proteinuria / prevention & control,  urine
Rats, Inbred SHR
Ventricular Function, Left / drug effects
Grant Support
Reg. No./Substance:
0/7-Ala-angiotensin (1-7); 0/Antihypertensive Agents; 0/Blood Glucose; 0/Cytokines; 0/Insulin; 0/Leptin; 0/Peptide Fragments; 0/angiotensin I (1-7); 11128-99-7/Angiotensin II; 50903-99-6/NG-Nitroarginine Methyl Ester; 62571-86-2/Captopril; 86-54-4/Hydralazine; 9041-90-1/Angiotensin I

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