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.