Document Detail


Cardiovascular effects of inhibition of renin-angiotensin-aldosterone system components in hypertensive rats given salt excess.
MedLine Citation:
PMID:  20118410     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study examined the role of the renin-angiotensin-aldosterone system (RAAS) in mediating cardiovascular and renal damage in spontaneously hypertensive rats (SHR) given salt excess. Since the circulating RAAS is inhibited in this model, it permits examination of the role of local tissue RAASs in mediating this injury. To this end, male 8-wk SHR were divided into 7 groups. The control group (C) received normal NaCl (0.6%) diet. All other groups were given 8% NaCl chow. In addition, group 2 was given placebo, group 3 the mineralocorticoid receptor blocker eplerenone (100 mg.kg(-1).day(-1)), group 4 the angiotensin converting enzyme inhibitor quinapril (3 mg.kg(-1).day(-1)), group 5 the angiotensin II type 1 receptor blocker candesartan (10 mg.kg(-1).day(-1)), and groups 6 and 7 eplerenone and either quinapril or candesartan. The treatments lasted 8 wk. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve, minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall were all adversely affected by salt loading. Left ventricular mass and fibrosis as well as proteinuria were also markedly increased by salt overload. Eplerenone induced only slight changes, whereas quinapril and candesartan normalized all indexes except MAP. Combination therapy also normalized all indexes, including MAP. These data suggest that 1) cardiovascular and renal damage induced by salt excess in the SHR were not pressure dependent; 2) mineralocorticoids were only marginally involved in this model; and 3) local tissue generation of angiotensin II may be, at least in part, responsible for the other adverse effects.
Authors:
Dinko Susic; Jasmina Varagic; Edward D Frohlich
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-29
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  298     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-22     Completed Date:  2010-04-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1177-81     Citation Subset:  IM    
Affiliation:
Ochsner Clinic Foundation, New Orleans, LA 70121, USA. dsusic@ochsner.org
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II Type 1 Receptor Blockers / pharmacology*
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Animals
Benzimidazoles / pharmacology
Blood Pressure / drug effects
Cardiomyopathies / chemically induced,  pathology
Cardiovascular System / drug effects,  physiopathology*
Hypertension / physiopathology*
Hypertrophy / chemically induced,  pathology
Kidney / blood supply
Male
Rats
Rats, Inbred SHR
Receptors, Mineralocorticoid / antagonists & inhibitors,  drug effects
Regional Blood Flow / drug effects
Renin-Angiotensin System / drug effects*,  physiology*
Sodium Chloride, Dietary / adverse effects,  pharmacology*
Spironolactone / analogs & derivatives,  pharmacology
Tetrahydroisoquinolines / pharmacology
Tetrazoles / pharmacology
Ventricular Dysfunction, Left / chemically induced
Chemical
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Benzimidazoles; 0/Receptors, Mineralocorticoid; 0/Sodium Chloride, Dietary; 0/Tetrahydroisoquinolines; 0/Tetrazoles; 0/eplerenone; 139481-59-7/candesartan; 52-01-7/Spironolactone; 82586-55-8/quinapril

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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