α 2 ‐Adrenoceptor and NPY receptor‐mediated contractions of porcine isolated blood vessels: evidence for involvement of the vascular endothelium

Enhanced contractions to the α 2 ‐adrenoceptor agonist UK14304 and neuropeptide Y (NPY) in the porcine ear artery can be uncovered by pharmacological manipulation. The aim of this study was to determine whether similar pharmacological manipulation can uncover enhanced contractions in the porcine splenic artery, and to determine whether the endothelium modulates these responses. UK14304 (0.3 μ M ) and NPY (0.1 μ M ) produced small contractions of the porcine splenic artery. After pre‐contraction of the tissue with U46619, followed by relaxation with forskolin, the responses to both UK14304 and NPY were enhanced. Enhanced contractions to both UK14304 and NPY were also obtained after relaxation with SNP. These results demonstrate that, as in the porcine ear artery, α 2 ‐adrenoceptors and NPY receptors are able to produce enhanced contractile responses through both adenylyl cyclase‐dependent and ‐independent signal transduction pathways. Removal of the endothelium had no significant effect on responses to UK14304 either alone or in the presence of U46619 and forskolin in the porcine splenic artery. On the other hand, responses to UK14304 after relaxation with SNP were reduced after endothelium‐denudation in both the porcine splenic artery and ear artery. Similar results were obtained with NPY in the porcine ear artery. In conclusion, enhanced contractile responses to UK14304 and NPY in the porcine splenic artery can be uncovered using methods similar to those employed in the porcine ear artery. Under certain conditions the responses to both agents are modulated by the endothelium. These data highlight further the similarities in the signal transduction pathways used by both α 2 ‐adrenoceptors and NPY receptors to induce vasoconstriction.British Journal of Pharmacology (1999) 128 , 1705–1712; doi: 10.1038/sj.bjp.0702979