Combination renin–angiotensin system blockade and angiotensin-converting enzyme 2 in experimental myocardial infarction: implications for future therapeutic directions

摘要: The RAS (renin-angiotensin system) is activated after MI (myocardial infarction), and blockade with ACEis [ACE (angiotensin-converting enzyme) inhibitors] or ARBs (angiotensin receptor blockers) slows but does not completely prevent progression to heart failure. Cardiac ACE increased leads the formation of vasoconstrictor AngII II). enzyme ACE2 also degrades generate vasodilator Ang-(1-7) [angiotensin-(1-7)]. Overexpression offers cardioprotective effects in experimental MI, there conflicting evidence as whether benefits are mediated through increasing MI. In present study, we assessed effect an ACEi ARB, alone combination, on cardiac a rat model. rats received vehicle, (ramipril; 1 mg/kg body weight), ARB (valsartan; 10 weight) combination (ramipril at weight valsartan orally for 28 days. Sham-operated were studied vehicle alone. LV (left ventricular) mass (P<0.0001), impaired contractility (P<0.05) gene protein expression (viable myocardium, P<0.05; border zone, P<0.001; infarct, P<0.05). Ramipril improved remodelling (P<0.05), no additional dual therapy. Although ramipril inhibited ACE, blocked angiotensin receptor, neither treatment nor augmented expression. These results suggest that up-regulation ACE2. Strategies do augment may be useful addition standard