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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:772.)
© 2005 American Heart Association, Inc.

Vascular Biology

B1 Kinin Receptor Does Not Contribute to Vascular Tone or Tissue Plasminogen Activator Release in the Peripheral Circulation of Patients With Heart Failure

Nicholas L.M. Cruden; George H. Tse; Keith A.A. Fox; Christopher A. Ludlam; Ian Megson; David E. Newby

From the Centre for Cardiovascular Science, University of Edinburgh, Royal Infirmary of Edinburgh, United Kingdom.

Correspondence to Dr N.L.M. Cruden, Centre for Cardiovascular Science, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom, EH16 4SB. E-mail nick.cruden{at}ed.ac.uk

Objective— Vascular expression of the B₁ kinin receptor is markedly upregulated with left ventricular dysfunction and angiotensin-converting enzyme (ACE) inhibition, but its function remains unclear. Inhibitors of ACE potentiate bradykinin-mediated B₂ receptor-dependent vasodilatation and tissue plasminogen activator (tissue-type plasminogen activator [t-PA]) release. We investigated the contribution of the B₁ receptor to the maintenance of vascular tone and t-PA release in patients with heart failure.

Methods and Results— Eleven patients were treated with enalapril (10 mg twice daily) or losartan (50 mg twice daily) in a randomized double-blind crossover trial. During week 6 of each treatment, patients received an intrabrachial infusion of Lys-des-Arg⁹-bradykinin (B₁ agonist; 1 to 10 nmol/min), bradykinin (30 to 300 pmol/min), Lys-[Leu⁸]-des-Arg⁹-bradykinin (B₁ antagonist; 1 to 10 nmol/min), and norepinephrine (60 to 540 pmol/min). Blood flow and t-PA release were measured using venous occlusion plethysmography and blood sampling. Bradykinin (P<0.001 for all), but not Lys-des-Arg⁹-bradykinin, caused vasodilatation and t-PA antigen and activity release. Norepinephrine (P<0.001), but not Lys-[Leu⁸]-des-Arg⁹-bradykinin, caused vasoconstriction. Compared with losartan, enalapril augmented bradykinin-mediated vasodilatation (P<0.05) and t-PA release (P<0.01 for all) but had no effect on B₁ receptor-mediated responses.

Conclusions— The B₁ kinin receptor does not have a major vasomotor or fibrinolytic role in patients with heart failure. Augmentation of kinin-mediated vasodilatation and t-PA release by ACE inhibition is restricted to the B₂ receptor.

In contrast to bradykinin, intra-brachial Lys-des-Arg⁹-bradykinin (B₁ agonist) and Lys-[Leu⁸]-des-Arg⁹-bradykinin (B₁ antagonist) had no effect on vascular tone or tissue plasminogen activator release in patients with heart failure treated with angiotensin-converting enzyme inhibition. The B₁ kinin receptor does not have a major vasomotor or fibrinolytic role in patients with heart failure.

Key Words: ACE inhibitors • bradykinin • heart failure • plasminogen activators • receptors

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