OBJECTIVE: The aim was to investigate the role of local formation of angiotensin II and bradykinin in the reduction of myocardial infarct size. METHODS: Bilaterally nephrectomised male mongrel dogs were used. Effects were compared of pretreatment with three inhibitors of angiotensin II forming enzyme-captopril (an angiotensin converting enzyme inhibitor), nafamostat (a serine protease inhibitor), and chymostatin (a cysteine protease inhibitor)--on left anterior descending coronary artery occlusion. Haemodynamic variables were monitored and blood was collected from the anterior interventricular vein and the aorta. Angiotensin I, angiotensin II, and bradykinin were measured by radioimmunoassay. After 90 min of occlusion, infarct sizes were determined by a macroscopic enzyme technique. RESULTS: Angiotensin II release into the anterior interventricular vein increased from 0.03(SEM 1.19) pg.min-1 (before coronary occlusion) to 4.64(1.37) pg.min-1 (n = 14, p < 0.05), while angiotensin I release and plasma renin activity remained unchanged. The increase in angiotensin II release was inhibited by nafamostat and chymostatin, but not by captopril. Bradykinin release increased from -3.18(2.72) (before coronary occlusion) to 34.7(12.3) pg.min-1 (n = 14 p < 0.05) by 30 min after occlusion. This increase was augmented by captopril, from 4.10(2.86) before occlusion to 97.8(39.6) pg.min-1 at 5 min after occlusion (n = 12, p < 0.05), but not by nafamostat or chymostatin. Infarct size was smaller (p < 0.05) in the captopril group than in the control group. CONCLUSIONS: Angiotensin II is locally produced in the ischaemic heart by both serine protease(s) and chymostatin inhibitable protease(s), but not by angiotensin converting enzyme. From the reduction in myocardial infarct size produced by angiotensin converting enzyme inhibition, it seems that bradykinin accumulation may play a more important role than the suppression of angiotensin II formation.
OBJECTIVE: The aim was to investigate the role of local formation of angiotensin II and bradykinin in the reduction of myocardial infarct size. METHODS: Bilaterally nephrectomised male mongrel dogs were used. Effects were compared of pretreatment with three inhibitors of angiotensin II forming enzyme-captopril (an angiotensin converting enzyme inhibitor), nafamostat (a serine protease inhibitor), and chymostatin (a cysteine protease inhibitor)--on left anterior descending coronary artery occlusion. Haemodynamic variables were monitored and blood was collected from the anterior interventricular vein and the aorta. Angiotensin I, angiotensin II, and bradykinin were measured by radioimmunoassay. After 90 min of occlusion, infarct sizes were determined by a macroscopic enzyme technique. RESULTS: Angiotensin II release into the anterior interventricular vein increased from 0.03(SEM 1.19) pg.min-1 (before coronary occlusion) to 4.64(1.37) pg.min-1 (n = 14, p < 0.05), while angiotensin I release and plasma renin activity remained unchanged. The increase in angiotensin II release was inhibited by nafamostat and chymostatin, but not by captopril. Bradykinin release increased from -3.18(2.72) (before coronary occlusion) to 34.7(12.3) pg.min-1 (n = 14 p < 0.05) by 30 min after occlusion. This increase was augmented by captopril, from 4.10(2.86) before occlusion to 97.8(39.6) pg.min-1 at 5 min after occlusion (n = 12, p < 0.05), but not by nafamostat or chymostatin. Infarct size was smaller (p < 0.05) in the captopril group than in the control group. CONCLUSIONS: Angiotensin II is locally produced in the ischaemic heart by both serine protease(s) and chymostatin inhibitable protease(s), but not by angiotensin converting enzyme. From the reduction in myocardial infarct size produced by angiotensin converting enzyme inhibition, it seems that bradykinin accumulation may play a more important role than the suppression of angiotensin II formation.
Authors: L J Dell'Italia; Q C Meng; E Balcells; C C Wei; R Palmer; G R Hageman; J Durand; G H Hankes; S Oparil Journal: J Clin Invest Date: 1997-07-15 Impact factor: 14.808