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

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.