Participation of angiotensin II and bradykinin in contractile function in dog stunned myocardium

Abstract

We examined the effects of enalapril and 4′-[(1,4′-dimethyl-2′-propyl-[2,6′-bi-1H-enzimidazole]-1′-yl)methyl]-[1,1′-biphenyl]-2-carboxylic acid (BIBR-277), an angiotensin II receptor antagonist, on contractile dysfunction in the stunned myocardium. Dogs were subjected to 20-min ligation of the coronary artery, followed by 60-min reperfusion. Saline, enalapril (1 mg/kg or 3 mg/kg), or BIBR-277 (3 mg/kg) was injected i.v. 10 min before ligation. d-Arginyl- l-arginlyl- l-prolyl- trans-4-hydroxy- l-prolylglycyl-3-(2-thienyl)- l-alanyl- l-seryl- d-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl- l-(2α, 3β, 7aβ)-octahydro-1H-indole-2-carbonyl- l-arginine (Hoe-140), a bradykinin B 2 receptor antagonist, at 300 μg/kg was injected i.v. 10 min before drug injection. Contractile function was assessed on the basis of percentage segment shortening (%SS). ATP levels were measured in 60-min reperfused hearts. %SS significantly decreased during ischemia, and recovered during reperfusion, although the %SS was significantly less than the pre-ischemic level. Both enalapril at either dose and BIBR-277 significantly enhanced %SS recovery during reperfusion, an effect which was associated with a tendency toward energy preservation. Hoe-140 completely abolished the effect of enalapril at either dose, while it did not modify that of BIBR-277. Inhibition of angiotensin II formation and bradykinin breakdown may be separately related to the improvement of myocardial stunning.