Effects of neuropeptide Y and calcitonin gene-related peptide on sheep coronary artery rings under oxygenated, hypoxic and simulated myocardial ischaemic conditions.

1. The effects of calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) were examined on sheep circumflex (2-2.5 mm o.d.) coronary artery rings, with and without endothelium, under oxygenated, hypoxic and simulated ischaemic conditions. The interaction between the vasoconstrictor effects of NPY and the thromboxane mimetic, U46619, was also studied. 2. Ischaemia was simulated by modification of the composition of the physiological salt solution by increasing potassium and H+, including lactate and reducing glucose and PO2. 3. Hypoxia alone and simulated ischaemia increased the maximum vasodilatation produced by CGRP. CGRP (30 nM) abolished and markedly reduced the contraction that was induced by hypoxia and simulated ischaemia respectively. 4. Hypoxia increased and simulated ischaemia reduced the contractile response to NPY in endothelium intact rings. When the endothelium was removed, NPY caused a contraction under ischaemic conditions only. The hypoxic and ischaemic-induced contractions were augmented by NPY (30 nM). 5. In the rings containing endothelium, NPY enhanced the contraction caused by U46619 during hypoxia only. In endothelium-denuded preparations, NPY increased or partially restored the contraction caused by U46619. 6. These results show that the responsiveness of coronary artery rings isolated from sheep to either CGRP or NPY is modified by hypoxia or simulated myocardial ischaemia.