Neuropeptide Y (NPY) and receptor subtypes Y1, Y2 and Y5 are present in the heart. NPY constricts coronary arteries, possibly contributing to myocardial ischaemia. No studies have examined the effects of NPY and antagonists during ischaemia-reperfusion. We hypothesised that the administration of Y1, Y2 and Y5 receptor antagonists would be cardioprotective.Methods
Male Sprague-Dawley rat hearts were Langendorff perfused and subjected to 35 min left coronary artery occlusion (CAO). The receptor antagonists were used: Y1 BMS193885; Y2 BIIE0246; Y5 L152804. In the first series of experiments, NPY or NPY receptor antagonists were administered (all at 10 nM) from 5 min prior to CAO until 10 min after reperfusion. In a second series NPY or antagonists were given only during the early ischaemic period, from 5 min prior to CAO until 10 min after CAO. Reperfusion was continued for 120 min after which hearts were sectioned and stained with triphenyltetrazolium chloride. Infarct size was expressed as a percentage of the ischaemic risk zone.Results
Series 1. Administration of NPY and the antagonists throughout ischaemia and early reperfusion limited infarct size. Series 2. Administration of NPY only during early ischaemia was not protective. Although Y1 and Y5 receptor antagonists were potently protective in this setting, Y2 receptor antagonism had no effect.Conclusions
The data suggest that NPY receptor antagonism limits infarct size. Activation of Y2 receptor may be deleterious during late ischaemia or early reperfusion. Under some circumstances, NPY may be cardioprotective. Further studies are required to elucidate the role of NPY in preconditioning and the effectiveness antagonists as adjuncts to reperfusion.