EFFECT OF ANGIOTENSIN-(1-7) ON REPERFUSION ARRHYTHMIAS IN ISOLATED RAT HEARTS

There is increasing evidence that angiotensin-(1-7) (Ang-(1-7)) is an endogenous biologically active component of the renin-angiotensin syst em (RAS). In the present study, we investigated the effects of Ang-(1- 7) on reperfusion arrhythmias in isolated rat hearts. Isolated rat hea rts were perfused with two different media, i.e., Krebs-Ringer (2.52 m M CaCl2) and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2). In hearts perfused with Krebs-Ringer, Ang-(1-7) produced a concentration-dependent (27-2 10 nM) reduction in coronary flow (25% reduction at highest concentrat ion), while only slight and variable changes in contraction force and heart rate were observed. Under the same conditions, angiotensin II (A ng II; 27 and 70 nM) produced a significant reduction in coronary flow (39% and 48%, respectively) associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs- Ringer solution, perfusion with Ang-(1-7) or Ang II at 27 nM concentra tion produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs-Ringer, Ang- (1-7) produced a significant enhancement of reperfusion arrhythmias re vealed by an increase in the incidence and duration of ventricular tac hycardia and ventricular fibrillation (more than 30-min duration). The facilitation of reperfusion arrhythmias by Ang-(1-7) was associated w ith an increase in the magnitude of the decreased force usually observ ed during the postischemic period. The effects of Ang-(1-7) were aboli shed in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The e ffect of Ang II (27 nM) was similar but less pronounced than that of A ng-(I-7) at the same concentration. These results indicate that the he art is a site of action for Ang-(1-7) and suggest that this heptapepti de may be involved in the mediation of the cardiac effects of the RAS.