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 α2‐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 μM prazosin, neither UK‐14304 (0.01 – 3 μM) nor oxymetazoline (0.01 – 30 μM) caused a significant contraction of the porcine isolated rectal artery, a preparation with a low density of α2‐adrenoceptors. In the presence of a combination of U46619 and forskolin, however, both agonists produced concentration‐dependent contractions. Pretreatment with phenoxybenzamine (3 μM) abolished responses to UK‐14304, but left those elicited by oxymetazoline largely unaffected. The putative I3 imidazoline antagonist 2‐(2,3 dihydro‐2‐benzofuranyl)‐2‐imidazole (KU‐14R, 10 μM) 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 I3 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