The effect of a neuropeptide YY1 receptor antagonist in patients with angina pectoris

Aims Neuropeptide Y (NPY) is a potent vasoconstrictor released during sympathetic activation that may be involved in myocardial ischaernia. We examined the effect of a Y1 receptor antagonist on haemodynamic and ischaemic responses to exercise in patients with coronary artery disease. Methods and results Eighty-two evaluable mate patients were included in a randomized, double blind, two-way crossover study with a low dose (6.7 mug/kg/min; n=59) and a high dose (13.3 mug/kg/min; n=23) of the Y1 receptor antagonist AR-H040922 given as infusions for 2 h or placebo. Myocardial ischaernia 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. (C) 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.