Vascular effects of apelin in vivo in man

J Am Coll Cardiol. 2008 Sep 9;52(11):908-13. doi: 10.1016/j.jacc.2008.06.013.


Objectives: 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, (Pyr(1))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 (Pyr(1))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-N(G)-monomethylarginine [8 mumol/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 (Pyr(1))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). (Pyr(1))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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apelin
  • Blood Pressure
  • Forearm / blood supply*
  • Heart Rate
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Male
  • Protein Isoforms / physiology
  • Regional Blood Flow
  • Vasodilation / physiology*
  • Vasomotor System / physiology*


  • APLN protein, human
  • Apelin
  • Intercellular Signaling Peptides and Proteins
  • Protein Isoforms
  • apelin-13 peptide