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.


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.
Cruden
Nicholas L M
NL
Centre for Cardiovascular Science, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom, EH16 4SB. nick.cruden@ed.ac.uk
Tse
George H
GH
Fox
Keith A A
KA
Ludlam
Christopher A
CA
Megson
Ian
I
Newby
David E
DE
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
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