Abstract
Resveratrol (RES; trans-3,5,4′-trihydroxystilbene) has been shown to improve health and slow the progression of disease in various models. Several cardioprotective mechanisms have been identified including antioxidant, anti-inflammatory, and antifibrotic actions. Each of these actions is thought to have the ability to attenuate the pathophysiology underlying the deleterious cardiac structural remodeling that results from acute myocardial infarction (MI). Therefore, we evaluated the effect of resveratrol treatment on the progression of cardiac remodeling after MI. Four groups of rats (sham, n = 6; sham + RES, n = 21; MI, n = 26; MI + RES, n = 24) were treated for 13 weeks, starting 7 days before ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography revealed that resveratrol had no effect on MI-induced left-ventricular and left-atrial dilatation or reduction in left-ventricular fractional shortening. Consistent with these findings, resveratrol did not improve the deterioration of hemodynamic function or reduce infarct size at 12 weeks post-MI. Resveratrol-treated animals did, however, show preserved cardiac contractile reserve in response to dobutamine administration. Radioligand binding revealed that MI reduced β-adrenergic receptor density. Resveratrol administration increased β-adrenoceptor density, so that resveratrol-treated MI rats had β-adrenoceptor densities similar to normal rats. Real-time reverse transcription-polymerase chain reaction revealed that MI-induced changes in sarcoplasmic reticulum Ca2+-ATPase 2 and transforming growth factor β-1 expression were unaltered by resveratrol, whereas MI-induced increases in atrial natriuretic factor (ANF) and connective tissue growth factor (CTGF) expression were attenuated. Resveratrol treatment does not improve cardiac remodeling and global hemodynamic function post-MI but does preserve contractile reserve and attenuate ANF and CTGF up-regulation.
Footnotes
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This work was supported by the Canadian Institutes of Health Research and by the Quebec Heart and Stroke Foundation. B.B. received a Canadian Institutes of Health Research M.D./Ph.D. studentship. A.C. is a Chercheur-Boursier National of the “Fonds de la Recherche en Santé du Québec.” T.E.H. is a senior scholar of the Fonds de la Recherche en Santé du Québec and is supported by grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Québec.
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B.B. and A.M. contributed equally to this work.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.127548.
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ABBREVIATIONS: RES, resveratrol, trans-3,5,4′-trihydroxystilbene; MI, myocardial infarction; LAD, left anterior descending; LA, left atrium; LV, left ventricle; LVDD, left ventricular end-diastolic diameter; LVEDP, left ventricular end-diastolic pressure; Pmax, maximum generated pressure; +dP/dtmax, maximal rate of pressure development; –dP/dtmin, maximal rate of pressure relaxation; βAR, β-adrenergic receptor; RT, reverse transcription; PCR, polymerase chain reaction; ANF, atrial natriuretic factor; SERCA-2, sarcoplasmic reticulum Ca2+-ATPase 2; Col, collagen; TGFβ1, transforming growth factor β-1; CTGF, connective tissue growth factor; ANOVA, analysis of variance; DFn, degree of freedom in the numerator; DFd, degree of freedom in the denominator.
- Received June 21, 2007.
- Accepted September 14, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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