The effect of a neuropeptide Y Y1 receptor antagonist in patients with angina pectoris.
OBJECTIVE
Neuropeptide Y (NPY) is a potent vasoconstrictor released during sympathetic activation that may be involved in myocardial ischaemia. We examined the effect of a Y1 receptor antagonist on haemodynamic and ischaemic responses to exercise in patients with coronary artery disease.


RESULTS
Eighty-two evaluable male patients were included in a randomized, double blind, two-way crossover study with a low dose (6.7 microg/kg/min; n=59)and a high dose (13.3 microg/kg/min; n=23) of the Y1 receptor antagonist AR-H040922 given as infusions for 2h or placebo. Myocardial ischaemia during a symptom-limited exercise test was monitored by conventional ST-segment analysis and heart rate (HR)-adjusted ST changes including the ST/HR slope and ST/HR recovery. Administration of the high dose AR-H040922 attenuated systolic blood pressure by 6-11 mmHg (p<0.05) during and after exercise without affecting HR. None of the two doses of AR-H040922 influenced any of the ischaemic parameters or duration of exercise, however. The maximal increase in NPY was higher during AR-H040922 (p<0.05) compared with placebo.


CONCLUSIONS
Selective NPY Y1 receptor blockade attenuates the increase in blood pressure during exercise indicating a role for endogenous NPY in blood pressure regulation. Despite this effect, the Y1 receptor antagonist did not influence exercise-induced ischaemic parameters in patients with coronary artery disease.
Gullestad
L
L
Department of Cardiology Rikshospitalet University Hospital, Oslo, Norway.
Bjurø
T
T
Aaberge
L
L
Apelland
T
T
Skårdal
R
R
Kjekshus
E
E
Nordlander
M
M
Ablad
B
B
Pernow
J
J
D000328:Adult; D000368:Aged; D000577:Amides / Q000097:blood / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000097:blood
D000577:Amides; C420032:H 409-22; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor