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Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs
Author(s) -
Richard Vincent,
Ghaleh Bijan,
Berdeaux Alain,
Giudicelli JeanFrançois
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13908.x
Subject(s) - enalaprilat , angiotensin ii , medicine , antagonist , losartan , angiotensin ii receptor antagonist , ace inhibitor , angiotensin ii receptor type 1 , enalapril , cardiology , angiotensin converting enzyme , perfusion , saline , myocardial infarction , blood pressure , receptor
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 (AT 1 ) 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 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 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 triphenyltet‐razolium 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 AT 1 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.