| Angiotensin-(1-7) blockade attenuates captopril- or hydralazine-induced cardiovascular protection in spontaneously hypertensive rats treated with NG-nitro-L-arginine methyl ester. | |
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MedLine Citation:
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PMID: 21326110 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ibrahim F Benter; Mariam H M Yousif; Fatemah M Al-Saleh; Raj Raghupathy; Mark C Chappell; Debra I Diz |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 57 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-16 Completed Date: 2011-09-16 Revised Date: 2012-05-02 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 559-67 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin I
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antagonists & inhibitors*,
pharmacology Angiotensin II / administration & dosage, analogs & derivatives, pharmacology Animals 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 Male Myocardial Contraction / drug effects Myocardial Reperfusion Injury / physiopathology, prevention & control NG-Nitroarginine Methyl Ester / pharmacology Peptide Fragments / administration & dosage, antagonists & inhibitors*, pharmacology Perfusion Proteinuria / prevention & control, urine Rats Rats, Inbred SHR Ventricular Function, Left / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL-51952/HL/NHLBI NIH HHS; HL-56973/HL/NHLBI NIH HHS; P01 HL051952-18/HL/NHLBI NIH HHS; R01 HL056973-09/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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