| Title: |
Bradykinin: vasomotor tone and endogenous fibrinolysis in man |
| Authors: |
Witherow, Fraser Norman |
| Publisher Information: |
The University of Edinburgh |
| Publication Year: |
2007 |
| Collection: |
University of Edinburgh: Edinburgh Research Archive (ERA) |
| Description: |
Bradykinin is a nonapetide released into plasma during the contact phase of blood coagulation. It has a wide variety of physiological effects including vasodilatation, tissue-type plasminogen activator (t-PA) release, inflammatory mediator, ischaemic preconditioning and vasculogenesis. It is inactivated in plasma by angiotensinconverting enzyme (ACE). Inhibition of this enzyme has been shown to be beneficial in a variety of cardiovascular disorders including heart failure and hypertension, and it is clear that this benefit is not due entirely to reduction in the bioavailability of angiotensin II. We hypothesised that ; • bradykinin is a vasodilator and stimulates endothelial t-PA release via a specific receptor and that this effect is augmented by ACE inhibition ; • in patients with heart failure, bradykinin contributes to peripheral and systemic vascular tone during treatment with ACE inhibition. ; Forearm blood flow was measured using bilateral forearm plethysmography during intrabrachial drug infusion. Bilateral venous cannulae were inserted to perform blood sampling for estimation of plasma t-PA and plasminogen activator inhibitor 1 (PAI1) concentrations. Cardiac output was measured with pulmonary artery catheterisation. The novel peptide bradykinin receptor antagonist, B9340, was used to oppose the effects of bradykinin. ; Studies were performed in healthy volunteers ; • to demonstrate the pharmacodynamics of B9340 and to demonstrate the selectivity of B9340 in opposing bradykinin-induced t-PA release. ; • to demonstrate the safety and tolerability of systemic intravenous B9340 administration. ; Studies were performed in patients with heart failure ; • to demonstrate the effect of ACE inhibition on endothelial t-PA release. ; • to demonstrate the effect of bradykinin antagonism on peripheral and systemic vascular tone in patients treated with ACE inhibition and angiotensin receptor blockade. ; RESULTS In healthy volunteers ; • Bradykinin and substance P caused dose-dependent vasodilatation in the infused ... |
| Document Type: |
doctoral or postdoctoral thesis |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
Annexe Thesis Digitisation Project 2018 Block 17; Already catalogued; https://hdl.handle.net/1842/29426 |
| Availability: |
https://hdl.handle.net/1842/29426 |
| Accession Number: |
edsbas.B815F560 |
| Database: |
BASE |