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Title: The role of bradykinin in cardiovascular disease
Author: Witherow, F. N.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Bradykinin is a vasodilator and stimulates endothelial t-PA release via a specific receptor and that this effect is augmented by angiotensin converting enzyme inhibition; in patients with heart failure, bradykinin contributes to peripheral and systemic vascular tone during treatment with ACE inhibition. Bradykinin and substance P caused dose-dependent vasodilation in the infused forearm; B9340 caused a dose-dependent inhibition of bradykinin-induced forearm vasodilation and t-PA release; B9340 caused a reversible inhibition of bradykinin-induced vasodilation with a rapid onset and offset of action. In patients with heart failure: bradykinin and substance P caused dose-dependent vasodilation and release of t-PA from the infused forearm; long-term ACE inhibitor therapy caused an increase in forearm vasodilation (p<0.05) and t-PA release during bradykinin, but not substance P, infusion; incremental doses of B9340 caused a dose-dependent reduction in forearm blood flow (p<0.01); after withdrawal of ACE inhibitor therapy, B9340 produced no significant change in forearm blood flow; systemic intravenous B9340 administration resulted in greater mean arterial pressure and systemic vascular resistance, during ACE inhibitor therapy, compared with losartan therapy or placebo infusion. We have shown that bradykinin is a potent vasodilator that stimulates endogenous t-PA release and that these effects are receptor specific and can be blocked by a bradykinin receptor antagonist. We have also shown that bradykinin does not contribute to peripheral of systemic vascular tone in health but does contribute to peripheral and systemic vascular tone in patients with heart failure treated with chronic ACE inhibition. We believe this suggests that many of the beneficial actions of ACE inhibition are mediated through bradykinin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available