title: B1 kinin receptor does not contribute to vascular tone or tissue plasminogen activator release in the peripheral circulation of patients with heart failure.
abstract: 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.
  
  
  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 B(1) 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.
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom, EH16 4SB. nick.cruden@ed.ac.uk
authors.forename: Nicholas L M
authors.initials: NL
authors.lastname: Cruden
authors.forename: George H
authors.initials: GH
authors.lastname: Tse
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ludlam
authors.forename: Ian
authors.initials: I
authors.lastname: Megson
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
mesh_terms: D000293:Adolescent; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D065169:Bradykinin B1 Receptor Antagonists; D018592:Cross-Over Studies; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007609:Kallidin / Q000008:administration & dosage / Q000031:analogs & derivatives; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011247:Pregnancy; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000097:blood*; D014471:Umbilical Veins / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D065169:Bradykinin B1 Receptor Antagonists; D017395:Plasminogen Activator Inhibitor 1; D043783:Receptor, Bradykinin B1; C082229:bradykinin, Lys-Leu(8)-desArg(9)-; D007609:Kallidin; D004656:Enalapril; C052787:kallidin, des-Arg(10)-; D010959:Tissue Plasminogen Activator; D019808:Losartan