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Title: Inhibition of kinin metabolism and the role of the vascular B₁ kinin receptor in patients with congestive heart failure
Author: Cruden, Nicholas Le May
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Biological activity of kinin receptor agonists and antagonists was confirmed in human umbilical vein. Systemic bradykinin antagonism caused an increase in mean arterial pressure and systemic vascular resistance and attenuated the fall in pulmonary arterial and pulmonary arterial wedge pressures in patients treated with enalapril compared to losartan. Compared to placebo, thiorphan augmented the vasomotor and fibrinolytic actions of bradykinin in patients treated with chronic angiotensin-converting enzyme inhibition. B1 receptor agonism and antagonism had no effect on vascular tone or endothelial tissue plasminogen activator release in the presence or absence of angiotensin-converting enzyme inhibition. The B2 receptor agonist, bradykinin, caused vasodilatation and tissue plasminogen activator release and these effects were markedly augmented by angiotensin-converting enzyme inhibition. Conclusions: Bradykinin contributes to the systemic haemodynamic effects of long-term angiotensin-converting enzyme inhibition in patients with heart failure. Neutral endopeptidase contributes to the metabolism of bradykinin in patients with heart failure maintained on angiotensin-converting enzyme inhibitor therapy. Our findings may explain some of the apparent clinical differences between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, as well as the greater vasodepressor effect observed with combined angiotensin-converting enzyme and neutral endopeptidase inhibition when compared to angiotensin-converting enzyme inhibition alone. Finally, the B1 kinin receptor does not appear to have a major vasomotor or fibrinolytic role in patients with heart failure. Augmentation of kinin-mediated vasodilatation and tissue plasminogen activator release by angiotensin-converting enzyme inhibition is restricted to the B2 receptor.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available