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European Heart Journal 2003 24(12):1120-1127; doi:10.1016/S0195-668X(03)00209-4
Copyright © 2003 by the European Society of Cardiology.
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The effect of a neuropeptide Y Y1 receptor antagonist in patients with angina pectoris

L. Gullestada, T. Bjurøb, L. Aabergea, T. Apellanda, R. Skårdala, E. Kjekshusa, M. Nordlanderc, B. Åbladc and J. Pernowd,*

a Department of Cardiology Rikshospitalet University Hospital, Oslo, Norway
b Wallenberg Laboratory, Sahlgrens University Hospital, Gothenburg, Sweden
c AstraZeneca R & D, Mölndal, Sweden
d Department of Cardiology, Karolinska Hospital, Stockholm, Sweden

* Correspondence to: John Pernow, MD, PhD, Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden. Tel: +46 8 51775876; fax: +46 8 311044
E-mail address: john.pernow{at}ks.se

Received 27 November 2002; revised 21 February 2003; accepted 20 March 2003

Aims 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.

Methods and results Eighty-two evaluable male patients were included in a randomized, double blind, two-way crossover study with a low dose (6.7µg/kg/min; n=59)and a high dose (13.3µg/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 6–11mmHg (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.

Key Words: Coronary artery disease • exercise testing • myocardial ischaemia • peptides


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