COMPARISON OF THE EFFECTS OF EXP3174, AN ANGIOTENSIN-II ANTAGONIST AND ENALAPRILAT ON MYOCARDIAL INFARCT SIZE IN ANESTHETIZED DOGS

1 In order to determine whether the renin-angiotensin system is involv ed in myocardial ischaemia-reperfusion injury, we investigated and com pared the effects on infarct size of two different drugs which interfe re with this system, i.e., an angiotensin II (AT1) antagonist, EXP3174 , and an angiotensin 1-converting enzyme inhibitor (ACEI), enalaprilat in a canine model of ischaemia-reperfusion. 2 EXP3174 (0.1 mg kg-1, i .v. followed by 0.02 mg kg-1 h-1 for 5.5 h) and enalaprilat (0.3 mg kg -1, i.v. followed by 0.06 mg kg-1 h-1 for 5.5 h) were used in doses in ducing a similar level of inhibition (87 +/- 4 and 91 +/- 3%, respecti vely) of the pressor responses to angiotensin I. Control animals recei ved saline. 3 Infarct size and area at risk were quantified by ex vivo dual coronary perfusion with triphenyltetrazolium chloride and monast ral blue dye. Regional myocardial blood flows (ischaemic and nonischae mic, endocardial, epicardial) were assessed by the radioactive microsp here technique. 4 Both EXP3174 and enalaprilat induced a decrease in m ean arterial blood pressure. However, non significant changes in regio nal myocardial blood flows, whether ischaemic or nonischaemic, were ob served after administration of either the ACEI or the AT1 antagonist. 5 The size of the area at risk was similar in the three groups. By dir ect comparison, there were no significant differences between infarct sizes in the three groups. Furthermore, there was a close inverse rela tionship between infarct size and transmural mean collateral blood flo w in controls, and none of the treatments altered this correlation. Th us, neither EXP3174 nor enalaprilat limited infarct size. 6 These resu lts indicate that activation of the renin-angiotensin system does not contribute to myocyte death in this canine ischaemia/reperfusion model .