Vascular B1 kinin receptors in patients with congestive heart failure.
Animal models suggest a vasomotor role for the B1 kinin receptor in cardiovascular disease states. In patients with heart failure treated with angiotensin-converting enzyme inhibition (ACEi), or combined B1/B2 receptor antagonism, but not B2 receptor antagonism alone, causes vasoconstriction. However, B1 agonism has no effect on vasomotor or fibrinolytic function. Findings from transgenic animals lacking the B2 receptor suggest that these conflicting data may be explained by cross-talk between B1 and B2 receptors. We hypothesized that B1 stimulation causes vasodilatation and tissue plasminogen activator release in the human forearm when B2 receptor signaling is inhibited. Forearm blood flow was measured in 16 patients with heart failure receiving ACEi. In double-blinded crossover studies, intrabrachial Lys-[Leu8]-des-Arg9-bradykinin (B1 antagonist), lys-des-Arg9-bradykinin (B1 agonist), bradykinin (B2 agonist), and sodium nitroprusside (endothelium-independent vasodilator) were infused alone or with HOE-140 (B2 antagonist). HOE-140 did not affect basal vascular tone or t-PA release, but it abolished bradykinin-induced vasodilatation and t-PA release (P < 0.0001). Blood flow and t-PA release were unaffected by B1 agonism or antagonism in the presence and absence HOE-140. Our findings do not support a role for crosstalk between the B1 and B2 kinin receptors in the human peripheral circulation.
Lang
Ninian N
NN
Centre for Cardiovascular Science, University of Edinburgh, United Kingdom; and thedaggerDepartment of Cardiology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, United Kingdom. ninian.lang@ed.ac.uk
Cruden
Nicholas L
NL
Tse
George H
GH
Bloomfield
Peter
P
Ludlam
Christopher A
CA
Fox
Keith A
KA
Newby
David E
DE
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D007609:Kallidin / Q000031:analogs & derivatives / Q000494:pharmacology; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C082229:bradykinin, Lys-Leu(8)-desArg(9)-; D009599:Nitroprusside; D007609:Kallidin; C052787:kallidin, des-Arg(10)-; C065679:icatibant; D010959:Tissue Plasminogen Activator; D001920:Bradykinin