| Carvedilol prevents and reverses hypertrophy-induced cardiac dysfunction. | |
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MedLine Citation:
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PMID: 17551266 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Histological studies have provided evidence that carvedilol can prevent cardiac hypertrophy in spontaneously hypertensive-stroke prone rats (SP) fed a high-fat and -salt diet. However, the effects of carvedilol on cardiac function have not been studied in these animals. In addition, the ability of carvedilol to reverse established cardiac hypertrophy and dysfunction under these conditions remains to be determined. Here we have evaluated the ability of carvedilol to prevent and reverse cardiac hypertrophy and progressive dysfunction using echocardiography. METHODS: Two echocardiology studies were conducted to determine the effects of carvedilol treatment on cardiac hypertrophy and dysfunction. In the first prevention study, four groups of rats were evaluated. SP were fed a high-fat (24.5% in food) and high-salt (1% in water) diet (SFD) without (SP-SFD control group) or with carvedilol (SP-SFD carvedilol group; carvedilol concentration 2,400 parts per million) for 18 weeks. Carvedilol was administered in the food at an optimum concentration (i.e. known to provide clinically relevant blood concentrations and reduce cardiac hypertrophy determined from previous studies). In addition, SP and WKY rats were fed a normal diet (SP normal diet group and WKY normal diet group). These groups are known to not develop the same significant cardiac hypertrophy and dysfunction within this limited time of study, and provided two more normal control groups for comparison. In the second reversal study, one group of SP was fed SFD for 12 weeks (SP-SFD pretreatment period) to induce cardiac hypertrophy. Carvedilol (2,400 parts per million) was then added to the diet for an additional 6 weeks (SP-SFD carvedilol treatment period). RESULTS: In the first prevention study, carvedilol prolonged longevity (p < 0.05) and prevented left-ventricular hypertrophy and dysfunction (p < 0.05; SP-SFD control vs. SP-SFD carvedilol group). M-mode-measured and -calculated parameters demonstrated that carvedilol treatment in the SP-SFD carvedilol group prevented increases in left-ventricular wall thickness (p < 0.05) and decreases in diastolic chamber diameter and volume, stroke volume, ejection fraction and cardiac output (all p < 0.05) that occurred in the SP-SFD control group. Further, cardiac measurements in the SP-SFD carvedilol group were normalized to levels similar to those in the SP and WKY normal diet groups. All SFD-fed groups exhibited similar, significantly elevated blood pressure during the study. In the second reversal study, carvedilol treatment for 6 weeks reversed the cardiac hypertrophy and dysfunction that developed in SP-fed SFD for 12 weeks prior to carvedilol intervention. Under these conditions, carvedilol improved/normalized left-ventricular wall thickness, diastolic ventricular-chamber diameter and volume, stroke volume, ejection fraction and cardiac output (all p < 0.05). CONCLUSIONS: These data indicate that carvedilol provides protection from and facilitates reversal of progressive cardiac remodeling and dysfunction in this SP-SFD model of cardiac hypertrophy/heart failure. Since these effects occurred in the absence of effects on blood pressure, other known actions of carvedilol, especially its antioxidant activity, for example, may explain this significant cardiac protection. In addition, research using this SP-SFD model of cardiac hypertrophy/end-organ injury appears to translate well to human cardiovascular disease. |
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Authors:
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Frank C Barone; Robert N Willette; Allen H Nelson; Eliot H Ohlstein; David P Brooks; Robert W Coatney |
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2944766 - Physiological adaptation of the heart to pathological overloading. 1671186 - Do we need another antihypertensive agent? 18045706 - Cardiac abnormalities in mcleod syndrome. 2138116 - The heart in hypertension and arrhythmias. 7264506 - Wolff-parkinson-white syndrome: t wave abnormalities during normal pathway conduction. 6696286 - Ergonovine provocation in post partum myocardial infarction. |
Publication Detail:
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Type: Journal Article Date: 2007-06-04 |
Journal Detail:
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Title: Pharmacology Volume: 80 ISSN: 0031-7012 ISO Abbreviation: Pharmacology Publication Date: 2007 |
Date Detail:
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Created Date: 2007-08-08 Completed Date: 2007-10-04 Revised Date: 2013-05-28 |
Medline Journal Info:
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Nlm Unique ID: 0152016 Medline TA: Pharmacology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 166-76 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2007 S. Karger AG, Basel. |
Affiliation:
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High Throughput Biology, Discovery Research, King of Prussia, PA, USA. frank.c.barone@verizon.net |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Adrenergic beta-Antagonists / pharmacology* Animals Antioxidants / pharmacology* Carbazoles / pharmacology* Cardiomegaly / physiopathology, prevention & control*, ultrasonography Diet Disease Models, Animal Dose-Response Relationship, Drug Male Propanolamines / pharmacology* Rats Rats, Inbred SHR Rats, Inbred WKY Treatment Outcome Vasodilator Agents / pharmacology* Ventricular Remodeling / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Antagonists; 0/Antioxidants; 0/Carbazoles; 0/Propanolamines; 0/Vasodilator Agents; 0K47UL67F2/carvedilol |
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