Vascular effects of apelin in vivo in man

Alan G Japp, Nicholas L Cruden, David A B Amer, Vivienne K Y Li, Ewan B Goudie, Neil R Johnston, Sushma Sharma, Ilene Neilson, David J Webb, Ian L Megson, Andrew D Flapan, David E Newby

Research output: Contribution to journalArticlepeer-review


This study was designed to establish the direct vascular effects of apelin in vivo in man.Background Apelin is the endogenous ligand for the previously orphaned G-protein-coupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation.

Methods Vascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr1) apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr1) apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a "nitric oxide clamp" (nitric oxide synthase inhibitor, L-NG-monomethylarginine [8 mu mol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo.

Results Although sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr1) apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr1) apelin-13-mediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7).

Conclusions Although having no apparent effect on venous tone, apelin causes nitric oxide-dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis.
Original languageEnglish
Pages (from-to)908-913
Number of pages6
JournalJournal of the American College of Cardiology
Issue number11
Publication statusPublished - 9 Sep 2008


  • apelin
  • APJ receptor


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