Interaction of cholecystokinin (CCK-8) with agonist and antagonist of beta-adrenergic receptors in circulatory system of diabetic rats.

The interaction of C-terminal cholecystokinin octapeptide (CCK-8) with beta-adrenoceptors agonist (isoprenaline-ISO) and antagonist (propranolol) and their influence on arterial blood pressure and function of isolated heart in rats with streptozotocin-induced diabetes mellitus (DM) was studied. After blockade of beta-adrenoceptors with propranolol, the hypertensive effect of CCK-8 was observed in the control group but not in DM-group, whereas CCK-8 had no effect on arterial blood pressure in the both studied groups. Stimulation of beta-adrenoceptors with ISO exerted the hypotensive effect of CCK-8 similar as after administration of the amine alone in the control and diabetic rats. CCK-8 increased the cardiac contraction amplitude and had no effect on heart rate and coronary outflow in control hearts. The positive inotropic effect of the peptide was abolished in DM-group. After blockade of beta-adrenoceptors, CCK-8 decreased all studied parameters of isolated hearts, the effect was similar as after infusion of propranolol alone. In DM group, after blockade of beta-adrenoceptors CCK-8 evoked decrease in the cardiac contraction amplitude (as during infusion of propranolol) and heart rate (the effect was greater than that after beta-adrenoceptors antagonist). CCK-8 administrated with ISO increased amplitude, heart rate and decreased coronary outflow of isolated control heart as after administration of ISO alone: in DM-group only the positive inotropic effect was observed. DM modified the effect of CCK-8 in circulatory system of rats. CCK-8 evoked bradycardia independent of stimulation or blockade of beta-adrenoceptors, mainly in DM.