Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure.
BACKGROUND
Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure.


RESULTS
Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr(1))apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all P<0.0001). Vasodilatation to acetylcholine (P=0.01) but not apelin (P=0.3) or sodium nitroprusside (P=0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all P<0.05). Systemic infusions of (Pyr(1))apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all P<0.01) but increased heart rate only in control subjects (P<0.01).


CONCLUSIONS
Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure.
Japp
A G
AG
Department of Cardiology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK. alan.japp@ed.ac.uk
Cruden
N L
NL
Barnes
G
G
van Gemeren
N
N
Mathews
J
J
Adamson
J
J
Johnston
N R
NR
Denvir
M A
MA
Megson
I L
IL
Flapan
A D
AD
Newby
D E
DE
D000109:Acetylcholine / Q000008:administration & dosage; D002302:Cardiac Output / Q000187:drug effects*; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009599:Nitroprusside / Q000008:administration & dosage; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D017725:Ventricular Pressure / Q000187:drug effects
D036341:Intercellular Signaling Peptides and Proteins; D014665:Vasodilator Agents; C495199:apelin-13 peptide; D009599:Nitroprusside; D000109:Acetylcholine