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 secretion and vascular resistance in the isolated perfused rat pancreas. On insulin secretion, two imidazoline alpha(2)-adrenoceptor antagonists, efaroxan (1-100 mu M) and RX821002 (10 mu M), had a stimulating response; however, idazoxan, like the non-imidazoline alpha(2)-adrenoceptor antagonist yohimbine, was ineffective at 10 mu M. The oxazoline rilmenidine with alpha(2)-adrenergic activity at 10 mu M inhibited insulin release; this effect was reversed to a stimulation after the blockade of alpha(2)-adrenoceptors. Antazoline (1-10 mu M), an imidazoline devoid of alpha(2)-adrenergic activity, also had an insulin-releasing effect. On pancreatic vessels, all imidazolines tested (efaroxan, RX821002, antazoline and idazoxan), in contrast to yohimbine, induced vasoconstriction. Rilmenidine did not have a vasoconstrictor effect after blockade of alpha(2)-adrenoceptors. Furthermore, the efaroxan-induced insulin release or vasoconstriction was not affected by the blockade of alpha(2)- and alpha(1)-adrenoceptors. This study shows that imidazolines and derivatives are able to stimulate insulin release and induce vasoconstriction in the rat pancreas. These effects cannot be ascribed to an interaction with alpha-adrenoceptors but may involve different types of imidazoline sites.