P4.11 LOWER LIMB VASOMOTOR AND FIBRINOLYTIC EFFECTS OF KININ RECEPTOR AGONISTS IN MAN

Abstract

Background: Vascular B1 kinin receptor expression is upregulated in human atheroma and the presence of angiotensin-converting enzyme inhibition (ACEi), but its role in man remains unclear. We examined vasomotor and fibrinolytic responses to selective kinin receptor agonism in the human femoral circulation and correlated responses with femoral arterial plaque load. Methods: Femoral arterial cross sectional area, blood flow and plaque volume were determined using intravascular ultrasound and a Doppler Flowire during selective femoral arterial infusion of Lys-des-Arg9-Bradykinin (B1 agonist; 3, 10, 30 nmol/min), bradykinin (B2 agonist; 100, 300, 1000 pmol/min) and sodium nitroprusside (6, 12, 24 mcg/min) in eleven patients undergoing diagnostic coronary angiography, in the presence and absence of ACEi. Tissue plasminogen activator (t-PA) release was measured across the femoral vascular bed. Results: Mean femoral arterial plaque load was 7.0±0.9mm3 per mm of vessel. Bradykinin and nitroprusside caused dose-dependent increases in femoral blood flow (p<0.05). Bradykinin alone caused a dose-dependent increase in net t-PA release (p<0.05) that was augmented by ACEi (p<0.05). There were no correlations between femoral plaque load and bradykinin mediated vasodilatation or t-PA release. Lys-des-Arg9-Bradykinin had no effect on blood flow or t-PA release, irrespective of femoral arterial plaque load or ACEi. Conclusions: The vasomotor and fibrinolytic actions of bradykinin in the human lower limb are mediated solely by the B2 kinin receptor, irrespective of the presence of atheroma or ACEi. In keeping with previous data, bradykinin-mediated t-PA release was augmented in the presence of ACEi, consistent with its putative vascular protective effect.