1. In order to determine whether the renin-angiotensin system is involved in myocardial ischaemia-
reperfusion injury, we investigated and compared the effects on
infarct size of two different drugs which interfere with this system, i.e., an
angiotensin II (AT1) antagonist,
EXP3174, and an
angiotensin I-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 enalaprilate (0.3 mg kg-1, i.v. followed by 0.06 mg kg-1 h-1 for 5.5 h) were used in doses inducing a similar level of inhibition (87 +/- 4 and 91 +/- 3%, respectively) of the pressor responses to
angiotensin I. Control animals received saline. 3.
Infarct size and area at risk were quantified by ex vivo dual coronary perfusion with
triphenyltetrazolium chloride and
monastral blue dye. Regional myocardial blood flows (ischaemic and nonischaemic, endocardial, epicardial) were assessed by the radioactive
microsphere technique. 4. Both
EXP3174 and
enalaprilat induced a decrease in mean arterial blood pressure. However, non significant changes in regional myocardial blood flows, whether ischaemic or nonischaemic, were observed 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 direct comparison, there were no significant differences between
infarct sizes in the three groups. Furthermore, there was a close inverse relationship between
infarct size and transmural mean collateral blood flow in controls, and none of the treatments altered this correlation. Thus, neither
EXP3174 nor
enalaprilat limited
infarct size. 6. These results indicate that activation of the renin-angiotensin system does not contribute to myocyte death in this canine ischaemia/reperfusion model.