Evidence for a non-adrenoceptor, imidazoline-mediated contractile responseto oxymetazoline in the porcine isolated rectal artery

Imidazoline derivatives are known to elicit responses through both alpha (2 )-adrenoceptor and non-adrenoceptor, imidazoline sites, though as yet there are no examples of the latter on vascular smooth muscle. In the presence o f 0.3 muM prazosin, neither UK-14304 (0.01-3 muM) nor oxymetazoline (0.01-3 0 muM) caused a significant contraction of the porcine isolated rectal arte ry, a preparation with a low density of alpha (2)-adrenoceptors. In the pre sence of a combination of U46619 and forskolin, however, both agonists prod uced concentration-dependent contractions. Pretreatment with phenoxybenzami ne (3 muM) abolished responses to UK-14304, but left those elicited by oxym etazoline largely unaffected. The putative I-3 imidazoline antagonist 2-(2, 3 dihydro-2-benzofuranyl)-2-imidazole (KU-14R, 10 muM) caused a 6 fold righ tward displacement of the phenoxybenzamine-insensitive concentration - resp onse curve to oxymetazoline. Our data indicates that non-adrenoceptor, imid azoline sites, pharmacologically similar to the I-3 imidazoline site on isl et cells, mediate vasoconstriction in the porcine isolated rectal artery.