Reversal of Early Metabolic Dysfunction in Hypertensive Rat Left-Ventricular Myocytes by Angiotensin-Converting Enzyme Inhibition

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概要

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• We evaluated the effects of angiotensin-converting enzyme (ACE) inhibition on metabolic changes in myocardial organelles, myocardial hypertrophy, and interstitial fibrosis in the early stage of hypertension. An ACE inhibitor, imidapril (2.5mg/kg per day), a calcium-channel blocker, diltiazem (30mg/kg per day), or vehicle was given to spontaneously hypertensive rats (SHRs) from 10 to 18 weeks of age. Single myocytes were isolated enzymatically from the left ventricles of these SHRs and normotensive Wistar-Kyoto (WKY) controls at 18 weeks of age. In single ventricular myocytes, enzyme activities in the sarcoplasmic reticulum (SR) and the sarcolemma (SL) and the mitochondrial respiratory control ratio (RCR) were determined. In 18-week-old SHRs receiving vehicle, myocardial hypertrophy and interstitial fibrosis developed, and SR Ca2+ ATPase activity and the mitochondrial RCR were significantly lower and SL Na+, K+-ATPase activity was significantly higher than in age-matched WKYs. However, compared with diltiazem, imidapril was better able to prevent the development of myocardial hypertrophy and interstitial fibrosis, to improve SR Ca2+-ATPase activity and the mitochondrial RCR, and to increase SL Na+, K+-ATPase activity. These results suggest that ACE inhibition can prevent the development of morphologic changes associated with hypertension-induced left ventricular remodeling, such as myocardial hypertrophy and interstitial fibrosis, and can counteract ongoing dysfunction of organelle metabolism early in the development of hypertension.

著者

• KONNO Noburu

  Third Department of Internal Medicine, Showa University School of Medicine

• Watanabe Takuya

  Third Department of Internal Medicine

• Yanagishita Toshikuni

  Third Department Of Internal Medicine Showa University School Of Medicine.

• Katagiri Takashi

  Third Department Inter Nat Medicine Showa University

• Geshi Eiichi

  Third Department Of Internal Medicine Showa University School Of Medicine

• GESHI Eiichi

  Third Department of Internal Medicine, Showa University School of Medicine

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