Journal of Cardiac Failure Vol. 3 No. 1 1997 Angiotensin and Bradykinin Peptides in Rats With Myocardial Infarction ANN-MAREE DUNCAN,* LOUISE M. BURRELL, 1" A T H E N A KLADIS,* DUNCAN J. CAMPBELL* Fitzroy, Heidelberg, Victoria, Australia ABSTRACT Background: Angiotensin II (Ang II) stimulates cardiac hypertrophy and fibrosis, whereas bradykinin [BK-(1-9)] has cardioprotective actions and reduces infarct size following myocardial infarction. Methods and ResuRs: We investigated whether myocardial infarction and cardiac failure are associated with changes in circulating and tissue levels of angiotensin and bradykinin peptides. Myocardial infarction was produced in rats by coronary artery ligation and confirmed by elec- trocardiogram. Ang H, Ang I, BK-(I-9), and its metabolite BK-(1-7) were measured 1, 2, 3, 7, and 28 days after myocardial infarction. In comparison with sham operated rats, myocardial infarction reduced blood pressure and body weight, and produced cardiac hypertrophy and car- diac failure. Myocardial infarction increased plasma renin and ACE activity, reduced plasma angiotensinogen, and increased Ang II levels in plasma, aorta, kidney, and lung. Ang [I levels in whole cardiac ventricles were similar in infarct and sham operated rats, but were positively correlated with heart weight/body weight ratio in infarct rats 3, 7, and 28 days after infarction. In a separate study of cardiac regions, Ang II levels were similar in infarct mad sham operated rats, except at 7 days post surgery when fight ventficular Ang II levels were higher in infarct rats. In infarct rats, Ang II levels were higher in the right ventricle and in the infarct than in the non-infarcted left ventricle at 7 days, but these differences were not apparent at 28 days after infarction. BK-(I-9) levels were increased in the heart and lung on days 2 and 3 post infarc- tion, but not in the aorta or kidney. A decrease in BK-(1-7)/BK-(1-9) ratio suggested reduced metabolism of BK-(1-9) to BK-(1-7) in infarcted hearts. Conclusions: The transient activation of the circulating renin angiotensin system, and increased Ang Ii levels in the aorta, kidney, and lung may contribute to the systemic responses to myocardial infarction and cardiac failure. The correlations between cardiac Ang II levels and heart weight/body weight ratio noted for whole cardiac ventricles support a role for local Ang II levels in the process of myocardial remodeling post infarction. The increased cardiac BK-(1-9) levels in the acute phase of myocardial infarction were consistent with a role for this peptide in cardioprotection and limitation of infarct size. Key Words: angiotensin, bradykinin, myocardial infarction, cardiac hypertrophy, cardiac failure. Myocardial infarction of moderate to large degree invokes a complex series of compensatory responses in the heart and circulatory system, culminating in scar for- From *St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia, and ?Department of Medicine, Austin and Repatriation Med- ical Centre, Heidelberg, Victoria, Australia. Funded by grants from the National Health and Medical Research Council of Australia, the National Heart Foundation of Australia, and from Servier Laboratories. Manuscript received Oct. 8, 1996; revised manuscript received Feb. 6, 1997; revised manuscript accepted Feb. 6, 1997. Reprint requests: D. J. Campbell, MD, St. Vincent's Institute of Med- ical Research, 41 Victoria Parade, Fitzroy, Victoria, Australia, 3065. marion, left ventricular remodeling with chamber dilata- tion, hypertrophy and fibrosis of the surviving myo- cardium, and progressive deterioration of left ventricular function (1,2). Both angiotensin II (Ang II) and bradykinin-(1-9) [BK-(1-9)] have important cardiac actions and may participate in responses to myocardial infarction. Ang II stimulates cardiac hypertrophy and fibrosis (3-8), whereas BK-(I-9) has cardioprotective actions and reduces infarct size following myocardial infarction (%14). Myocardial infarction is associated with activation of the circulating renin angiotensin system (15). Moreover, several lines of evidence suggest increased 41