EFFECTS OF IMIDAZOLINES AND DERIVATIVES ON INSULIN-SECRETION AND VASCULAR-RESISTANCE IN PERFUSED RAT PANCREAS

The effects of imidazolines and derivatives were studied on insulin se cretion and vascular resistance in the isolated perfused rat pancreas. On insulin secretion, two imidazoline alpha(2)-adrenoceptor antagonis ts, efaroxan (1-100 mu M) and RX821002 (10 mu M), had a stimulating re sponse; however, idazoxan, like the non-imidazoline alpha(2)-adrenocep tor antagonist yohimbine, was ineffective at 10 mu M. The oxazoline ri lmenidine with alpha(2)-adrenergic activity at 10 mu M inhibited insul in release; this effect was reversed to a stimulation after the blocka de of alpha(2)-adrenoceptors. Antazoline (1-10 mu M), an imidazoline d evoid of alpha(2)-adrenergic activity, also had an insulin-releasing e ffect. On pancreatic vessels, all imidazolines tested (efaroxan, RX821 002, antazoline and idazoxan), in contrast to yohimbine, induced vasoc onstriction. Rilmenidine did not have a vasoconstrictor effect after b lockade of alpha(2)-adrenoceptors. Furthermore, the efaroxan-induced i nsulin release or vasoconstriction was not affected by the blockade of alpha(2)- and alpha(1)-adrenoceptors. This study shows that imidazoli nes and derivatives are able to stimulate insulin release and induce v asoconstriction in the rat pancreas. These effects cannot be ascribed to an interaction with alpha-adrenoceptors but may involve different t ypes of imidazoline sites.