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(Hypertension. 1997;30:383.)
© 1997 American Heart Association, Inc.

Articles

Contractile Systolic and Diastolic Dysfunction in Renin-Induced Hypertensive Cardiomyopathy

Markus Flesch; Frank Schiffer; Oliver Zolk; Yigal Pinto; Stephan Rosenkranz; Claudia Hirth-Dietrich; Georg Arnold; Martin Paul; Michael Böhm

From the Klinik III für Innere Medizin (M.F., F.S., O.Z., S.R., M.B.) and the Institut für Pathologie (G.A.) der Universität zu Köln, Cologne; the Institut für Klinische Pharmakologie der Freien Universität Berlin, Universitätsklinikum Benjamin Franklin (Y.P., M.P.); and the Institut für Pharmakologische Forschung der Bayer AG, Wuppertal (C.H.-D.), Germany.

Abstract The present study investigated whether functional, molecular, and biochemical alterations occurring in chronic heart failure can already be detected in compensated hypertensive cardiac hypertrophy. Force of contraction (isolated papillary muscle strip preparations), sarcoplasmic reticulum (SR) protein and myosin heavy chain isoform expression (Northern and Western blot analysis), myocardial fibrosis (collagen stains, hydroxyproline quantification), myocardial renin mRNA (RT-PCR), and angiotensin II levels and plasma aldosterone concentrations (radioimmunoassay) were studied in hypertrophied myocardium from transgenic rats harboring the mouse Ren-2d gene. Contraction and relaxation velocities of isolated papillary muscle strips were significantly reduced in cardiac hypertrophy. The ß-/-myosin heavy chain ratio was significantly increased in the hypertrophied left ventricles, whereas SR Ca²⁺-ATPase (SERCA 2a) and phospholamban mRNA and protein levels were significantly decreased. The decrease in SERCA 2a was more pronounced than the decrease in phospholamban levels. There was no increased myocardial fibrosis. Left ventricular myocardial renin mRNA and angiotensin II concentrations, as well as plasma aldosterone levels, were higher in transgenic than in control rats. In hypertensive cardiac hypertrophy, myosin heavy chain isoform shift and reduction of SR protein levels are related to systolic and diastolic dysfunction, respectively. These alterations precede the development of myocardial fibrosis. Increased myocardial renin mRNA and angiotensin II concentrations suggest that an activated tissue renin-angiotensin system might contribute to these alterations. Since the alterations in compensated cardiac hypertrophy apparently precede those in chronic heart failure, they might accelerate the transition from hypertrophy to failure and could therefore be targets for pharmacological interventions.

Key Words: hypertrophy • heart failure • hypertension, genetic • renin-angiotensin system • sarcoplasmic reticulum

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