Evidence for a non‐adrenoceptor, imidazoline‐mediated contractile response to oxymetazoline in the porcine isolated rectal artery

Imidazoline derivatives are known to elicit responses through both α 2 ‐adrenoceptor and non‐adrenoceptor, imidazoline sites, though as yet there are no examples of the latter on vascular smooth muscle. In the presence of 0.3 μ M prazosin, neither UK‐14304 (0.01 – 3 μ M ) nor oxymetazoline (0.01 – 30 μ M ) caused a significant contraction of the porcine isolated rectal artery, a preparation with a low density of α 2 ‐adrenoceptors. In the presence of a combination of U46619 and forskolin, however, both agonists produced concentration‐dependent contractions. Pretreatment with phenoxybenzamine (3 μ M ) abolished responses to UK‐14304, but left those elicited by oxymetazoline largely unaffected. The putative I 3 imidazoline antagonist 2‐(2,3 dihydro‐2‐benzofuranyl)‐2‐imidazole (KU‐14R, 10 μ M ) caused a 6 fold rightward displacement of the phenoxybenzamine‐insensitive concentration – response curve to oxymetazoline. Our data indicates that non‐adrenoceptor, imidazoline sites, pharmacologically similar to the I 3 imidazoline site on islet cells, mediate vasoconstriction in the porcine isolated rectal artery. British Journal of Pharmacology (2001) 132 , 1359–1363; doi: 10.1038/sj.bjp.0703949