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Vascular effects of apelin in vivo in man.

Abstract：

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.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Japp AG,Cruden NL,Amer DA,Li VK,Goudie EB,Johnston NR,Sharma S,Neilson I,Webb DJ,Megson IL,Flapan AD,Newby DE

doi

10.1016/j.jacc.2008.06.013

subject

Has Abstract

pub_date

2008-09-09 00:00:00

pages

908-13

issue

11

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(08)02153-0

journal_volume

52

pub_type

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