Vascular effects of apelin in vivo in man.
OBJECTIVE
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.
Japp
Alan G
AG
Centre for Cardiovascular Science, University of Edinburgh, Chancellor's Building, Edinburgh, United Kingdom. alan.japp@ed.ac.uk
Cruden
Nicholas L
NL
Amer
David A B
DA
Li
Vivienne K Y
VK
Goudie
Ewan B
EB
Johnston
Neil R
NR
Sharma
Sushma
S
Neilson
Ilene
I
Webb
David J
DJ
Megson
Ian L
IL
Flapan
Andrew D
AD
Newby
David E
DE
D000328:Adult; D000073861:Apelin; D001794:Blood Pressure; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D020033:Protein Isoforms / Q000502:physiology; D012039:Regional Blood Flow; D014664:Vasodilation / Q000502:physiology*; D014666:Vasomotor System / Q000502:physiology*
C115436:APLN protein, human; D000073861:Apelin; D036341:Intercellular Signaling Peptides and Proteins; D020033:Protein Isoforms; C495199:apelin-13 peptide