Abstract 3625: Angiotensin II Receptor Blockade Improves Endogenous Coronary Fibrinolytic Function in Patients with Coronary Artery Disease
Background: The renin-angiotensin system plays an important role in the regulation of vascular fibrinolytic balance. Bradykinin (BK) is an endothelium-dependent coronary vasodilator and a potent stimulator for coronary release of tissue-type plasminogen activator (tPA). We examined chronic effects of losartan on coronary vasomotor and fibrinolytic function in patients with coronary artery disease and hypertension.
Methods: Sixteen patients underwent coronary angiography and percutaneous transluminal coronary intervention for the left circumflex or right coronary artery and were readmitted after 6 months for follow-up coronary arteriography. All patients were randomly assigned to two groups: 8 patients were treated with losartan (50 mg/day) for about 6 months (Lo group) and 8 were treated with calcium channel blockers (Ca group). Graded doses of BK (0.2, 0.6, 2.0 μg/min) were infused into the left coronary artery. Coronary blood flow (CBF) in the left anterior descending artery was evaluated by measuring Doppler flow velocity. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS) for measurement of tPA antigen. Net coronary release of tPA antigen was determined as a CS-Ao gradient × CBF × [(100-Hematocrit) / 100].
Results: Age, gender, coronary risk factors, and baseline coronary diameters and flows were comparable in the two groups. Graded doses of BK caused dose-dependent increases in CBF, the CS-Ao gradient, and net tPA release in all patients. In the Lo group, increases in %CBF (2.0 μg/min: 238 ± 24 to 292 ± 35 %), the CS-Ao tPA gradient (2.0 μg/min: 7.3 ± 1.1 to 9.1 ± 1.2 ng/ml), and net tPA release (2.0 μg/min: 286 ± 35 to 341 ± 42 ng/min) induced by BK were significantly greater after than before the losartan treatment (p<0.05, respectively). In the Ca group, these parameters did not change during the follow-up period. Coronary vasomotor responses induced by nitroglycerin (0.25 mg) or papaverine (12 mg) did not change during the follow-up period in either group.
Conclusion: Losartan improves endothelium-dependent coronary fibrinolytic function, which may contribute to suppressing future coronary thrombotic events.