Effects of angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptides in rats with myocardial infarction.

Angiotensin-converting enzyme (ACE) inhibitors reduce myocardial remodeling and improve cardiac function after myocardial infarction. We investigated whether the beneficial effects of ACE inhibition were associated with changes in the levels of angiotensin and bradykinin peptides in blood, heart, lung, aorta, and kidney. Rats subjected to coronary artery ligation and selected by ECG criteria to have moderate to large myocardial infarctions (mean size, 38%) were administered perindopril (0, 20, 200, and 2,000 micrograms/kg/day) in their drinking water from the second day after surgery for 26 days. Perindopril caused a dose-related decrease in blood pressure and inhibited the development of both cardiac hypertrophy (estimated by heart weight/body weight ratio) and cardiac failure (estimated by lung weight/body weight ratio). Perindopril inhibited plasma ACE activity and increased plasma renin, with an associated decrease in plasma angiotensinogen. Plasma and all tissues showed a marked reduction in angiotensin II/angiotensin I ratio, indicating effective inhibition of ACE in plasma and tissues. Whereas heart, lung, and kidney showed dose-related decreases in angiotensin II (Ang II) levels, plasma and aortic levels of Ang II were not altered by perindopril. Perindopril increased blood bradykinin levels but did not increase bradykinin levels in heart, lung, aorta, or kidney. Heart showed a 45% increase in bradykinin levels at the highest dose of perindopril, which did not achieve statistical significance, although perindopril reduced the bradykinin(1-7)/ bradykinin-(1-9) ratio in heart, indicating inhibition of cardiac metabolism of bradykinin by perindopril. By contrast, perindopril reduced bradykinin levels in lung. These data support a role for reduced blood pressure and cardiac Ang II levels in mediating the effects of ACE inhibition after myocardial infarction but do not support a role for tissue bradykinin in this process.