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Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction

Daniela Fraccarollo, PhD^*, Paolo Galuppo, PhD^*, Steven Hildemann, MD, Michael Christ, MD, Georg Ertl, MD^* and Johann Bauersachs, MD^*,*

^* Medizinische Klinik der Julius-Maximilians-Universität Würzburg, Würzburg, Germany
Pharmacia Corp., Peapack, New Jersey, USA
Klinik für Innere Medizin-Kardiologie Phillips-Universität Marburg, Marburg, Germany

View larger version (29K): [in a new window]   Figure 1 (A) The time constant of left ventricular pressure decay (Tau), and (B) left ventricular (LV) pressure–volume (P-V) loops and left ventricular end-diastolic volume measured in vivo with conductance catheter in sham-operated rats (Sham) and in rats with extensive myocardial infarction (P MI): Effects of aldosterone receptor inhibition (E), ACE inhibition (T), or combined aldosterone and ACE inhibition (E+T). Mean ± SEM (n = 6 to 12). *p < 0.05 versus Sham; p < 0.05, p < 0.001, p = 0.0001 versus P MI; #p < 0.05 versus E MI; **p = 0.059 versus T MI.

View larger version (18K): [in a new window]   Figure 2 Ratios of messenger ribonucleic acid expression ß-myosin heavy chain (MHC) to -MHC and of atrial natriuretic factor (ANF) to glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) in the left ventricle of sham-operated rats (Sham) and in the noninfarcted left ventricular myocardium of rats with extensive myocardial infarction (P MI): Effects of aldosterone receptor inhibition (E), ACE inhibition (T), or combined aldosterone and ACE inhibition (E+T). Mean ± SEM (n = 5 to 7). *p < 0.05 versus Sham; p < 0.05, p < 0.005, p = 0.0001 versus P MI; #p < 0.05 versus E MI.

View larger version (18K): [in a new window]   Figure 3 Type I collagen messenger ribonucleic acid levels, collagen concentration, and matrix metalloproteinase (MMP)-13 protein expression in the left ventricle of sham-operated rats (Sham) and in the noninfarcted left ventricular myocardium of rats with extensive myocardial infarction (P MI): Effects of aldosterone receptor inhibition (E), ACE inhibition (T), or combined aldosterone and ACE inhibition (E+T). Mean ± SEM (n = 5 to 11). *p < 0.05 versus Sham; p < 0.05, p < 0.01, p < 0.001 versus P MI. GAPDH = glyceraldehyde-3-phosphate-dehydrogenase.

View larger version (23K): [in a new window]   Figure 4 Protein expression of angiotensin II type 1 (AT1) receptor, sarcoplasmic-reticulum calcium (SERCA2) ATPase, and phosphorylated endothelial nitric oxide synthase (eNOS) in the left ventricle of sham-operated rats (Sham) and in the noninfarcted left ventricular myocardium of rats with extensive myocardial infarction (P MI): Effects of aldosterone receptor inhibition (E), ACE inhibition (T), or combined aldosterone and ACE inhibition (E+T). Mean ± SEM (n = 7 to 11). *p < 0.05 versus Sham; p < 0.05, p < 0.005 versus P MI.