Vascular B1 kinin receptors in patients with congestive heart failure

Lang, N. N. , Cruden, N. L., Tse, G. H., Bloomfield, P., Ludlam, C. A., Fox, K. A. and Newby, D. E. (2008) Vascular B1 kinin receptors in patients with congestive heart failure. Journal of Cardiovascular Pharmacology, 52(5), pp. 438-444. (doi: 10.1097/FJC.0b013e31818c66cb) (PMID:19033823)

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Abstract

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.

Item Type:Articles
Additional Information:This work was supported by a Bristol-Myers Squibb Cardiovascular Prize Fellowship (NNL) and a British Heart Foundation Project Grant (PG/02/092/14228).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Newby, Professor David and Lang, Dr Ninian
Authors: Lang, N. N., Cruden, N. L., Tse, G. H., Bloomfield, P., Ludlam, C. A., Fox, K. A., and Newby, D. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Cardiovascular Pharmacology
Publisher:Lippincott, Williams & Wilkins
ISSN:0160-2446
ISSN (Online):1533-4023

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