Changes in cardiac ANG II postmyocardial infarction in rats: effects of nephrectomy and ACE inhibitors

We evaluated in rats the time course of changes in cardiac versus plasma AN G I and II postmyocardial infarction (MI) and the effects of nephrectomy an d angiotensin-converting enzyme (ACE) inhibitors on the early changes post- MI. Acute coronary artery ligation was induced in conscious rats using the two-stage model, and plasma and cardiac tissue were obtained shortly (6 h, 1 and 3 days) and chronically (1, 4, and 8-9 wk) after MI. In an additional group of rats, bilateral nephrectomy was performed 18 h before the coronar y artery ligation, and samples were obtained at 6 h post-MI. Furthermore, i n two additional groups of rats, treatment with enalapril and quinapril was started 3 days before the ligation, and samples were obtained at 1 or 3 da ys post-MI. In these groups of rats, plasma and left ventricular (LV) (infa rct and infarct free) ANG; I and II were measured by RIA after separation o n HPLC. In control rats, plasma ANG I and II showed a clear increase at 6 h post-MI but subsequently only minor increases were observed. In contrast, LV ANG II showed major increases at 6 h and 1 day post-MI, which had return ed to normal by 3 days in the infarct-free LV and after 1(-2) wk in the inf arct LV. LV ANG I showed a more gradual increase and remained elevated in t he infarct up to 8-9 wk. Nephrectomy preceding the MI lowered ANG I and II in plasma but enhanced their increases in the heart at 6 h post-MI. Both AC E inhibitors decreased plasma ANG II associated with large increases in pla sma ANG I. They also inhibited the increases in LV ANG II in both the infar ct and infarct-free LV at 1 and 3 days post-MI with however no significant increase in LV ANG I. In conclusion, induction of a MI in conscious rats le ads to rapid and marked, but only short-lived, increases in cardiac tissue ANG II in both the infarct and infarct-free parts of the LV. Pretreatment w ith ACE inhibitors, but not nephrectomy, blocks this increase. Local produc tion appears to play a major role in the increases in cardiac ANG II post-M I.