Brachial artery flow-mediated vasodilation is correlated with coronary vasomotor and fibrinolytic responses induced by bradykinin

Abstract

Endothelium plays a key role in the regulation of not only vascular tone but also thrombosis and fibrinolysis. Brachial flow-mediated vasodilation (FMD) provides a noninvasive method of assessing coronary endothelial dysfunction. However, no data are available on the relationship between brachial FMD and coronary fibrinolytic activity. Thus, we examined the relationship between brachial FMD and coronary vasomotor and fibrinolytic function. Brachial FMD by reactive hyperemia was defined as a change in diameter relative to the baseline as measured using high-resolution ultrasound. Coronary blood flow (CBF) responses to bradykinin (BK) were analyzed using Doppler flow velocity measurement. Coronary release of tissue-type plasminogen activator (tPA) antigen was determined as the transcardiac tPA gradient x [CBF x (100 - hematocrity 100)]. In 77 patients with normal coronary arteries, BK caused dose-dependent increases in CBF, transcardiac tPA gradient, and coronary tPA release. Among them, brachial FMD, the BK-induced CBF increase, and the coronary tPA release induced by BK in 14 diabetic subjects were lower than those in 63 non-diabetic subjects (p < 0.05, respectively). Brachial FMD correlated with the CBF increase, transcardiac tPA gradient (0.2 microg/min: r = 0.25; 0.6 microg/min: r = 0.43; 2.0 microg/min: r = 0.34; p < 0.05, respectively), and coronary tPA release (0.2 microg/min: r = 0.24; 0.6 microg/min: r = 0.44; 2.0 microg/min: r = 0.32; p < 0.05, respectively) in response to BK. Brachial FMD correlated significantly with coronary endothelial function and fibrinolytic activity in response to BK. Type 2 diabetes impaired coronary and brachial endothelium-dependent vasodilation and coronary fibrinolytic activity.