Interaction between the renin-angiotensin system (RAS), the KKS and fibrinolytic system. There is evidence that fibrinolytic balance is regulated by the RAS and the KKS. ACE is strategically poised to control fibrinolytic balance by promoting the breakdown of bradykinin and the conversion of Ang I to Ang II. Ang II causes the release of PAI-1 thus inhibiting fibrinolysis. Bradykinin stimulates t-PA release through its B2 receptor. ACE inhibition decreases PAI-1 antigen levels and increases endothelial t-PA release through endogenous bradykinin. In addition, ACE inhibition enhances exogenous bradykinin-mediated vasodilation and t-PA release. The augmentation of bradykinin-induced vasodilation, the increase in t-PA and the decrease in PAI-1 described with ACE inhibition in patients with ischemic heart disease may contribute to the primary mechanism of the anti-ischemic effects associated with chronic ACE inhibitor therapy. We have demonstrated that inpatients undergoing coronary artery bypass grafting (CABG) requiring CPB, not only did ACE inhibition increase fibrinolytic activity by decreasing PAI-1 antigen and increasing t-PA activity, but also enhanced the kinin response. Increased PAI-1 concentrations in the perioperative period are associated with acute vein graft thrombosis. Thus, ACE inhibitors have a potential to reduce the risk of acute graft thrombosis through their effects on Ang II generation by attenuating the PAI-1 response after CABG. As opposed to the beneficial effects of ACE inhibition on PAI-1, the augmentation of the kinin response during CPB may have detrimental effects including increased fibrinolysis with consequent bleeding and hypotension. The effect of angiotensin II type 1 (AT1) receptor antagonist on the fibrinolytic response to CPB is not known. Inpatients with essential hypertension AT1 receptor antagonist decreases PAI-1 antigen in some but not other studies. In Specific Aim 1 we will test the hypothesis that angiotensin-converting enzyme inhibitors and AT1 receptor antagonist modulate the fibrinolytic and inflammatory response to CPB differently.