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.