Robin, J; Kharbanda, R; Mclean, P; Campbell, R; Vallance, P; (2003) Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. Circulation , 107 (7) 954 - 959.
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BACKGROUND: Systemic hypotension as a consequence of vascular dysfunction is a well-recognized and important feature of critical illness. Although serine protease activation has been implicated as a cause of vascular dysfunction in systemic inflammation, the mechanism is unknown. Recently, a class of receptors with an entirely novel mechanism of action, protease-activated receptors (PARs), has been identified that would explain the link between protease activation and systemic hypotension. Our aim was to test the hypothesis that in vivo activation of protease-activated receptor 2 (PAR-2) in humans would mediate vasodilatation. METHODS AND RESULTS: For these first-in-human studies, an activating peptide for the human PAR-2 receptor was synthesized and administered to healthy volunteers. Using both the dorsal hand vein technique and forearm plethysmography, we studied the effects of PAR-2 activation in human blood vessels and investigated the mechanism of vasodilation. Activation of PAR-2 receptors in vivo dilated human blood vessels in a dose-dependent manner, and the effects were reduced by inhibition of both nitric oxide and prostanoid synthesis CONCLUSIONS: These findings demonstrate that serine protease activity can cause human vasodilation and provide a possible explanation of why serine protease activation in critical illness is associated with vascular dysfunction
|Title:||Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids|
|Additional information:||DA - 20030225 IS - 1524-4539 LA - eng PT - Journal Article RN - 0 (Cyclooxygenase Inhibitors) RN - 0 (Enzyme Inhibitors) RN - 0 (Oligopeptides) RN - 0 (Prostaglandins) RN - 0 (Receptor, PAR-2) RN - 0 (Receptors, Thrombin) RN - 0 (seryl-leucyl-isoleucyl--glycyl-lysyl-valine) RN - 10102-43-9 (Nitric Oxide) RN - 17035-90-4 (omega-N-Methylarginine) RN - 50-78-2 (Aspirin) RN - EC 126.96.36.199 (Nitric-Oxide Synthase) SB - AIM SB - IM|
|Keywords:||ACTIVATION, activity, antagonists & inhibitors, As, Aspirin, Blood, blood vessel, blood vessels, BLOOD-VESSELS, Class, Critical Illness, Cyclooxygenase Inhibitors, dorsal, Dose-Response Relationship, Drug, drug effects, DYSFUNCTION, effects, enzyme, Enzyme Inhibitors, Female, Forearm, Hand, HEALTHY, HUMANS, hypotension, HYPOTHESIS, ILLNESS, ILLNESSES, IM, in vivo, in-vivo, Inflammation, inhibition, INHIBITOR, INHIBITORS, LA, link, Male, MECHANISM, Methods, nitric oxide, nitric oxide synthase, NITRIC-OXIDE, Nitric-Oxide Synthase, novel, Oligopeptides, omega-N-Methylarginine, OXIDE, peptide, pharmacology, physiology, PLETHYSMOGRAPHY, Prostaglandins, PROSTANOID SYNTHESIS, Protease, Receptor, Receptor, PAR-2, receptors, Receptors, Thrombin, Result, Serine, Support, Non-U.S.Gov't, SYNTHASE, synthesis, SYSTEMIC, technique, Thrombin, Unknown, vascular, Vasodilation, vein, vessels, vivo|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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